Este articulo presenta el impacto econ6mico de un servicio de vigilancia para agentes antimicrobi... more Este articulo presenta el impacto econ6mico de un servicio de vigilancia para agentes antimicrobiales. Este servicio opera como parte del programa de revision de utilizaci6n de antimicrobiales y ademas ayuda a identificar los patrones de utilizaci6n de antimicrobiales en el hospital. En la farmacia se mantiene un record de todas las 6rdenes medicas para agentes antimicrobiales. Concurrentemente se lleva a cabo una revisi6n de utilizaci6n de agentes antimicrobiales especificos utilizando criterios preestablecidos. EI servicio de farmacia clinica interviene en todos los casos de utilizaci6n de antimicrobiales que no reunen los criterios. Desde los comienzos del servicio en septiembre de 1983 un total de 229 casos de uso de antimicrobiales han requerido la intervenci6n del servicio de farmacia clinica. La utilizaci6n de un regimen a un costo-eficacia mas ventajoso result6 en una economia de $65 381.00. Adernas se observ6 una reducci6n substancial en 10 que se gastaba en cefazolin luego de una educaci6n dirigida a promover el uso de este agente cada ocho horas en vez de cada seis horas. Con
Update in Intensive Care and Emergency Medicine, 1989
Benzodiazepines are among the most commonly used (sedative) drugs in intensive care due to their ... more Benzodiazepines are among the most commonly used (sedative) drugs in intensive care due to their favorable and dose-dependent (anxiolysis-sedation-hypnosis) clinical effects, and their mild cardiorespiratory side effects. Knowledge of their pharmacokinetics is indispensable for the selection of the most appropriate compound and for optimalization of long-term intravenous (i.v.) sedation. From the numerous benzodiazepines, only those available in parenteral formulations will be discussed in this chapter.
The pharmacokinetics of racemic baclofen as determined from plasma and urine data in six spastic ... more The pharmacokinetics of racemic baclofen as determined from plasma and urine data in six spastic patients treated with individualized oral doses, 30-80 mg daily, are presented. Peak plasma concentrations were achieved 1.9 h (+/- 0.7) after a dose. The fluctuation in the plasma concentration was great, ranging from 188 to 439%. The total body clearance averaged 175 ml.min-1 (+/- 44), plasma protein binding 35% (+/- 6). Baclofen was for the greater part excreted unchanged by the kidney, 65% (+/- 16). Its apparent renal equalled the creatinine clearance. The contribution of the renal clearance to the total body clearance can explain the previously described toxicity when renal impairment is present. The results agree with earlier reports on single doses in healthy subjects.
Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between inten... more Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between intensive care patients and volunteers or patients who are less severely ill, are described. Similar differences are observed for midazolam. In severely ill patients with normal renal function a wide interpatient variability of aminoglycoside half-life (t1/2) and increased distribution volume (Vd) are observed. This results in inadequate serum levels. A pharmacokinetic approach of drug dosing, based on serum concentrations in individual patients, is advised. For ceftazidime and ceftriaxone similar changes of t1/2 and Vd are observed. Since protein binding is frequently reduced in severely ill patients, the influence of altered binding of highly bound drugs on Vd and drug clearance is discussed. As both may be increased by reduced protein binding, the change of t1/2 to be expected is unpredictable. Dosing regimens should be based on pharmacokinetic data derived from patients whose severity of disease is comparable to that of the patients to be treated.
deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponenti... more deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponentially elim-Lignocaine is a suitable and safe agent for intravenous inated, with a t 1/2a of 4.3±2.1 min and a t 1/2 of regional anaesthesia (IVRA) with rapid onset of good 79.1±31.2 min. Total body clearance was 0.86±0.39L surgical anaesthesia. The onset time of the local min −1. Eight patients showed rapid release of liganaesthetic action of lignocaine was 11.2±5.1 min. nocaine from the exsanguinated area. In two patients Satisfactory surgical conditions, evidenced by good the systemic plasma concentration of lignocaine insensory blockade were achieved within 20 min, and creased more slowly than in the remaining eight. This no additional analgesics were required. There was no can be explained by a greater degree of lignocaine trend towards a fixed sequence, radial, median and absorbtion in the tissues of the arm. Pharmacokinetic ulnar in the development of sensory blockade. No constants after rapid and slow absorption were calpatient exhibited objective symptoms of toxicity, either culated. local or systemic, after release of the tourniquet, nor were there any subjective complaints. No changes in
Objective: The aim of this investigation was to compare the clinical effects and pharmacokinetics... more Objective: The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine and prilocaine in two groups of 15 patients undergoing axillary brachial plexus anaesthesia. Methods: The study had a randomised design. Patients were allocated to one of the two groups of 15. Each group received either lidocaine (600mg = 2.56 mmol/L + 5 mg/L adrenaline) or prilocaine (600mg = 2.72 mmol/L + 5 mg/L adrenaline), injected over a period of 30 seconds. Onset of the surgical analgesia was defined as the period from the end of the injection of the local anaesthetic to the loss of pinprick sensation in the distribution of all three nerves. Results: The mean onset time of surgical analgesia of both lidocaine and prilocaine was 10 minutes. Lidocaine was biexponentially eliminated with a rapid elimination phase half-life (t 1 ⁄2α) of 9.95 ± 14.3 minutes and a terminal elimination phase half-life (t 1 ⁄2β) of 2.86 ± 1.55 hours. Lidocaine was metabolised to MEGX (monoethylglycylxylidide); time to reach maximum plasma concentration (tmax) 2.3 ± 0.8 hours; maximum plasma concentration (Cmax) 0.32 ± 0.13 mg/L; t 1 ⁄2β 2.4 ± 2.4 hours. Lidocaine total body clearance was 67.8 ± 28.8 L/h. Prilocaine was rapidly and biexponentially eliminated with a t 1 ⁄2α of 9.4 ± 18.4 minutes and a t 1 ⁄2β of 2.12 ± 1.28 hours. The total body clearance of prilocaine (150 ± 53 L/h) was higher than that of lidocaine (p = 0.0255). Both compounds demonstrated a comparable volume of distribution (Vd), while the volume of distribution at steady-state (Vss) and the volume of distribution in the second compartment (Vβ) values of prilocaine were a factor of 1.6 higher than those of lidocaine (p < 0.001). Both compounds showed a comparable t 1 ⁄2α (p > 0.8) and a comparable t 1 ⁄2β (p = 0.26). Conclusion: Following axillary administration, lidocaine and prilocaine demonstrated similar pharmacokinetic behaviour and could therefore be used as the clinical preference for this regional anaesthesia technique.
Objective: To describe and examine the variations in the plasma concentrationtime curves and phar... more Objective: To describe and examine the variations in the plasma concentrationtime curves and pharmacokinetic parameters of mesalazine and its metabolite acetylmesalazine after administration of a 500mg gastroresistant tablet. Design and Study Participants: Plasma concentration data were obtained from a randomised, crossover bioequivalence study in 24 healthy volunteers. Methods: Participants received a single 500mg oral dose of two different formulations of gastroresistant (enteric-coated) mesalazine (formulations I and II). The formulations had similar dissolution profiles in phosphate buffer pH ranging from 6 to 8 in vitro, but were not bioequivalent. Plasma mesalazine and acetylmesalazine concentrations were determined according to validated methods involving high performance liquid chromatography analysis with coulometric detection. Results: There was a large variability in the release and absorption of mesalazine from both tablet formulations (I and II). Formulation I showed a small distinction between study participants who released/absorbed mesalazine monophasically and those who showed a biphasic absorption. Formulation II showed large differences in dissolution and absorption in vivo, resulting in almost 24 different curves, which could be grouped together in four gross types of drug release and pharmacokinetic behaviour. The four types of curves were characterised by the number and height of maximum plasma concentration (Cmax) values, namely Cmax1, Cmax1 < Cmax2, Cmax1 = Cmax2, and Cmax1 > Cmax2. The time to reach Cmax (tmax) values (tmax1 = 5.82 ± 0.77h and tmax2 = 11.5 ± 0.35h, p = 0.0357) coincided with lunch (4h) and dinner (11h) times. The true t*maxvalue, defined as tmax-lag time (tlag), for the six different forms of the plasma concentration-time curves, ranged between 1.17 and 4.94h with a percentage coefficient of variation (CV) of 30 to 100% (p = NS). After absorption mesalazine was metabolised into acetylmesalazine both in the gut wall and in the liver. Conclusions: Mesalazine, acting locally from the intestinal lumen on the inflamed mucosa, is rapidly absorbed in the upper part of the small intestine.
Objective: To investigate upper and lower limits in the renal clearance of acetylmesalazine and m... more Objective: To investigate upper and lower limits in the renal clearance of acetylmesalazine and mesalazine in humans. Study Design: Renal clearance data were obtained from four randomised, crossover bioequivalence studies and one intravenous administration study in 200 healthy volunteers. Methods: Study participants received tablets [gastroresistant single-dose 500mg (n = 24) and prolonged-release, single-dose 1000mg (n = 18); multiple-dose 1000mg three times daily for six days (n = 28)], suppositories [single-dose 500mg (n = 24)] and two intravenous administrations [100 and 250mg mesalazine (n = 6)]. In total 200 drug administrations were carried out, and plasma concentration-time curves and renal excretion rate-time profiles were obtained and analysed. Plasma and urine mesalazine and acetylmesalazine concentrations were determined according to validated methods using HPLC analysis with coulometric or mass spectrometric detection. Results: The metabolite acetylmesalazine was cleared renally via glomerular filtration and active tubular secretion resulting in renal clearance (CLR) values of 200 to 300 ml/min. The average renal clearance was 210 ml/min, 30% coefficient of variation (CV). Two phases in the upper limit of renal clearance can be distinguished, with renal clearance values of 430 and 340 ml/min, respectively. There was a lower limit of 120 ml/min. The CLR data of mesalazine demonstrated that after the saturable reabsorption process, mesalazine is filtered by the glomerulus, showing an upper limit of 100 ml/min and a lower limit of 1.5 ml/min. Variation in the renal clearance values of mesalazine and its metabolite acetylmesalazine are probably due to variations in cardiac output and hence renal blood flow. Combining the CLR data of mesalazine and acetylmesalazine showed that the saturable tubular reabsorption of mesalazine can also be explained as renal acetylation of mesalazine, resulting in the low CLR of mesalazine and the high CLR of acetylmesalazine.
The aim of this study was to investigate the disposition kinetics and renal clearance of propofol... more The aim of this study was to investigate the disposition kinetics and renal clearance of propofol (2,6-di-isopropylphenol) and its metabolites (propofolglucuronide and 1 ,4-quinolconjugate) in surgical patients after a short-duration infusion (30 minutes). Two half-life (tI / 2) values could be distinguished in the elimination of propofol and each of its metabolites. The distribution half-life (tl/,a) differed significantly from the elimination half-life (tl /,6) [7.6 ± 3.3 minutes and 119 ± 30.7 minutes, respectively ; p = 0.0003]. The calculated tll,a and tl/,~ values for each metabolite differed significantly (for propofolglucuronide, p = 0.0017; and for 1,4-quinolconjugate, p = 0.0185). The apparent tl/,absorption of both metabolites was similar and reflected the tl;,formation (80 VS 59 minutes, respectively). The volumes of distribution of propofol in the central compartment (V 1; 34.4 ± l2.0L) differed from the volume of distribution in the second compartment
(i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achi... more (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin. (ii) Six groups of five patients participated in the study. The first three groups (A-C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D-F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously. (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients. (iv) Large inter-individual variation in bone concentration was observed. (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.
Archives of Orthopaedic and Traumatic Surgery, 1981
150 gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 yea... more 150 gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 years and with severely impaired kidney function. Frequent determination of gentamicin plasma concentrations and renal functions were possible. The plasma concentration reached a plateau at approx. 3 micrograms/ml. No accumulation of gentamicin in plasma occurred.
The purpose of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in... more The purpose of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in 10 male patients after injection of a high dose (731 mg) of racemic R,S-mepivacaine for a combined psoas compartment/sciatic nerve block. Arterial blood samples were taken, and the plasma concentrations of the stereoisomers R(+)and S(-)-mepivacaine were measured by means of high-performance liquid chromatography (HPLC) with a Qliral AGP column. The S(-) isomer reached higher plasma concentrations than the R(+) isomer. The maximal plasma concentration (G) of R(+) was 1.54 2 0.34 pg/mL, whereas that of the S(-) isomer was 2.34 * 0.51 p@mL (P = O.OOO50). The time at which C, , was reached (T-J was identical for both isomers, The area under the plasma concentration-time m e from t = 0 to infinity (AUCm) of S(-)-mepivacaine was almost double that of R(+)-mepivacaine. The elimination half-life (Tm) was identical for both isomers (3 h), which means that the calculated total body clearance and the calculated steady-state volume of the distribution of R(+) are, respectively, 1.7 and 1.5 times larger than that of the S(-) isomer. We conclude that the plasma concentrations of the S(-)mepivacaine isomer were higher than those of the R(+) isomer because of a smaller volume of distribution and a slower total body clearance. (Anesth Analg 1992,7575-80) epivacaine is a racemic mixture of R(+)-and S(-)-mepivacaine, with the S(-) the more (5). The aim of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in 10 patients Accepkd for publication
Este articulo presenta el impacto econ6mico de un servicio de vigilancia para agentes antimicrobi... more Este articulo presenta el impacto econ6mico de un servicio de vigilancia para agentes antimicrobiales. Este servicio opera como parte del programa de revision de utilizaci6n de antimicrobiales y ademas ayuda a identificar los patrones de utilizaci6n de antimicrobiales en el hospital. En la farmacia se mantiene un record de todas las 6rdenes medicas para agentes antimicrobiales. Concurrentemente se lleva a cabo una revisi6n de utilizaci6n de agentes antimicrobiales especificos utilizando criterios preestablecidos. EI servicio de farmacia clinica interviene en todos los casos de utilizaci6n de antimicrobiales que no reunen los criterios. Desde los comienzos del servicio en septiembre de 1983 un total de 229 casos de uso de antimicrobiales han requerido la intervenci6n del servicio de farmacia clinica. La utilizaci6n de un regimen a un costo-eficacia mas ventajoso result6 en una economia de $65 381.00. Adernas se observ6 una reducci6n substancial en 10 que se gastaba en cefazolin luego de una educaci6n dirigida a promover el uso de este agente cada ocho horas en vez de cada seis horas. Con
Update in Intensive Care and Emergency Medicine, 1989
Benzodiazepines are among the most commonly used (sedative) drugs in intensive care due to their ... more Benzodiazepines are among the most commonly used (sedative) drugs in intensive care due to their favorable and dose-dependent (anxiolysis-sedation-hypnosis) clinical effects, and their mild cardiorespiratory side effects. Knowledge of their pharmacokinetics is indispensable for the selection of the most appropriate compound and for optimalization of long-term intravenous (i.v.) sedation. From the numerous benzodiazepines, only those available in parenteral formulations will be discussed in this chapter.
The pharmacokinetics of racemic baclofen as determined from plasma and urine data in six spastic ... more The pharmacokinetics of racemic baclofen as determined from plasma and urine data in six spastic patients treated with individualized oral doses, 30-80 mg daily, are presented. Peak plasma concentrations were achieved 1.9 h (+/- 0.7) after a dose. The fluctuation in the plasma concentration was great, ranging from 188 to 439%. The total body clearance averaged 175 ml.min-1 (+/- 44), plasma protein binding 35% (+/- 6). Baclofen was for the greater part excreted unchanged by the kidney, 65% (+/- 16). Its apparent renal equalled the creatinine clearance. The contribution of the renal clearance to the total body clearance can explain the previously described toxicity when renal impairment is present. The results agree with earlier reports on single doses in healthy subjects.
Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between inten... more Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between intensive care patients and volunteers or patients who are less severely ill, are described. Similar differences are observed for midazolam. In severely ill patients with normal renal function a wide interpatient variability of aminoglycoside half-life (t1/2) and increased distribution volume (Vd) are observed. This results in inadequate serum levels. A pharmacokinetic approach of drug dosing, based on serum concentrations in individual patients, is advised. For ceftazidime and ceftriaxone similar changes of t1/2 and Vd are observed. Since protein binding is frequently reduced in severely ill patients, the influence of altered binding of highly bound drugs on Vd and drug clearance is discussed. As both may be increased by reduced protein binding, the change of t1/2 to be expected is unpredictable. Dosing regimens should be based on pharmacokinetic data derived from patients whose severity of disease is comparable to that of the patients to be treated.
deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponenti... more deflation of the tourniquet. After releasing the tourniquet lignocaine is rapidly and biexponentially elim-Lignocaine is a suitable and safe agent for intravenous inated, with a t 1/2a of 4.3±2.1 min and a t 1/2 of regional anaesthesia (IVRA) with rapid onset of good 79.1±31.2 min. Total body clearance was 0.86±0.39L surgical anaesthesia. The onset time of the local min −1. Eight patients showed rapid release of liganaesthetic action of lignocaine was 11.2±5.1 min. nocaine from the exsanguinated area. In two patients Satisfactory surgical conditions, evidenced by good the systemic plasma concentration of lignocaine insensory blockade were achieved within 20 min, and creased more slowly than in the remaining eight. This no additional analgesics were required. There was no can be explained by a greater degree of lignocaine trend towards a fixed sequence, radial, median and absorbtion in the tissues of the arm. Pharmacokinetic ulnar in the development of sensory blockade. No constants after rapid and slow absorption were calpatient exhibited objective symptoms of toxicity, either culated. local or systemic, after release of the tourniquet, nor were there any subjective complaints. No changes in
Objective: The aim of this investigation was to compare the clinical effects and pharmacokinetics... more Objective: The aim of this investigation was to compare the clinical effects and pharmacokinetics of lidocaine and prilocaine in two groups of 15 patients undergoing axillary brachial plexus anaesthesia. Methods: The study had a randomised design. Patients were allocated to one of the two groups of 15. Each group received either lidocaine (600mg = 2.56 mmol/L + 5 mg/L adrenaline) or prilocaine (600mg = 2.72 mmol/L + 5 mg/L adrenaline), injected over a period of 30 seconds. Onset of the surgical analgesia was defined as the period from the end of the injection of the local anaesthetic to the loss of pinprick sensation in the distribution of all three nerves. Results: The mean onset time of surgical analgesia of both lidocaine and prilocaine was 10 minutes. Lidocaine was biexponentially eliminated with a rapid elimination phase half-life (t 1 ⁄2α) of 9.95 ± 14.3 minutes and a terminal elimination phase half-life (t 1 ⁄2β) of 2.86 ± 1.55 hours. Lidocaine was metabolised to MEGX (monoethylglycylxylidide); time to reach maximum plasma concentration (tmax) 2.3 ± 0.8 hours; maximum plasma concentration (Cmax) 0.32 ± 0.13 mg/L; t 1 ⁄2β 2.4 ± 2.4 hours. Lidocaine total body clearance was 67.8 ± 28.8 L/h. Prilocaine was rapidly and biexponentially eliminated with a t 1 ⁄2α of 9.4 ± 18.4 minutes and a t 1 ⁄2β of 2.12 ± 1.28 hours. The total body clearance of prilocaine (150 ± 53 L/h) was higher than that of lidocaine (p = 0.0255). Both compounds demonstrated a comparable volume of distribution (Vd), while the volume of distribution at steady-state (Vss) and the volume of distribution in the second compartment (Vβ) values of prilocaine were a factor of 1.6 higher than those of lidocaine (p < 0.001). Both compounds showed a comparable t 1 ⁄2α (p > 0.8) and a comparable t 1 ⁄2β (p = 0.26). Conclusion: Following axillary administration, lidocaine and prilocaine demonstrated similar pharmacokinetic behaviour and could therefore be used as the clinical preference for this regional anaesthesia technique.
Objective: To describe and examine the variations in the plasma concentrationtime curves and phar... more Objective: To describe and examine the variations in the plasma concentrationtime curves and pharmacokinetic parameters of mesalazine and its metabolite acetylmesalazine after administration of a 500mg gastroresistant tablet. Design and Study Participants: Plasma concentration data were obtained from a randomised, crossover bioequivalence study in 24 healthy volunteers. Methods: Participants received a single 500mg oral dose of two different formulations of gastroresistant (enteric-coated) mesalazine (formulations I and II). The formulations had similar dissolution profiles in phosphate buffer pH ranging from 6 to 8 in vitro, but were not bioequivalent. Plasma mesalazine and acetylmesalazine concentrations were determined according to validated methods involving high performance liquid chromatography analysis with coulometric detection. Results: There was a large variability in the release and absorption of mesalazine from both tablet formulations (I and II). Formulation I showed a small distinction between study participants who released/absorbed mesalazine monophasically and those who showed a biphasic absorption. Formulation II showed large differences in dissolution and absorption in vivo, resulting in almost 24 different curves, which could be grouped together in four gross types of drug release and pharmacokinetic behaviour. The four types of curves were characterised by the number and height of maximum plasma concentration (Cmax) values, namely Cmax1, Cmax1 < Cmax2, Cmax1 = Cmax2, and Cmax1 > Cmax2. The time to reach Cmax (tmax) values (tmax1 = 5.82 ± 0.77h and tmax2 = 11.5 ± 0.35h, p = 0.0357) coincided with lunch (4h) and dinner (11h) times. The true t*maxvalue, defined as tmax-lag time (tlag), for the six different forms of the plasma concentration-time curves, ranged between 1.17 and 4.94h with a percentage coefficient of variation (CV) of 30 to 100% (p = NS). After absorption mesalazine was metabolised into acetylmesalazine both in the gut wall and in the liver. Conclusions: Mesalazine, acting locally from the intestinal lumen on the inflamed mucosa, is rapidly absorbed in the upper part of the small intestine.
Objective: To investigate upper and lower limits in the renal clearance of acetylmesalazine and m... more Objective: To investigate upper and lower limits in the renal clearance of acetylmesalazine and mesalazine in humans. Study Design: Renal clearance data were obtained from four randomised, crossover bioequivalence studies and one intravenous administration study in 200 healthy volunteers. Methods: Study participants received tablets [gastroresistant single-dose 500mg (n = 24) and prolonged-release, single-dose 1000mg (n = 18); multiple-dose 1000mg three times daily for six days (n = 28)], suppositories [single-dose 500mg (n = 24)] and two intravenous administrations [100 and 250mg mesalazine (n = 6)]. In total 200 drug administrations were carried out, and plasma concentration-time curves and renal excretion rate-time profiles were obtained and analysed. Plasma and urine mesalazine and acetylmesalazine concentrations were determined according to validated methods using HPLC analysis with coulometric or mass spectrometric detection. Results: The metabolite acetylmesalazine was cleared renally via glomerular filtration and active tubular secretion resulting in renal clearance (CLR) values of 200 to 300 ml/min. The average renal clearance was 210 ml/min, 30% coefficient of variation (CV). Two phases in the upper limit of renal clearance can be distinguished, with renal clearance values of 430 and 340 ml/min, respectively. There was a lower limit of 120 ml/min. The CLR data of mesalazine demonstrated that after the saturable reabsorption process, mesalazine is filtered by the glomerulus, showing an upper limit of 100 ml/min and a lower limit of 1.5 ml/min. Variation in the renal clearance values of mesalazine and its metabolite acetylmesalazine are probably due to variations in cardiac output and hence renal blood flow. Combining the CLR data of mesalazine and acetylmesalazine showed that the saturable tubular reabsorption of mesalazine can also be explained as renal acetylation of mesalazine, resulting in the low CLR of mesalazine and the high CLR of acetylmesalazine.
The aim of this study was to investigate the disposition kinetics and renal clearance of propofol... more The aim of this study was to investigate the disposition kinetics and renal clearance of propofol (2,6-di-isopropylphenol) and its metabolites (propofolglucuronide and 1 ,4-quinolconjugate) in surgical patients after a short-duration infusion (30 minutes). Two half-life (tI / 2) values could be distinguished in the elimination of propofol and each of its metabolites. The distribution half-life (tl/,a) differed significantly from the elimination half-life (tl /,6) [7.6 ± 3.3 minutes and 119 ± 30.7 minutes, respectively ; p = 0.0003]. The calculated tll,a and tl/,~ values for each metabolite differed significantly (for propofolglucuronide, p = 0.0017; and for 1,4-quinolconjugate, p = 0.0185). The apparent tl/,absorption of both metabolites was similar and reflected the tl;,formation (80 VS 59 minutes, respectively). The volumes of distribution of propofol in the central compartment (V 1; 34.4 ± l2.0L) differed from the volume of distribution in the second compartment
(i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achi... more (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin. (ii) Six groups of five patients participated in the study. The first three groups (A-C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D-F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously. (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients. (iv) Large inter-individual variation in bone concentration was observed. (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.
Archives of Orthopaedic and Traumatic Surgery, 1981
150 gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 yea... more 150 gentamicin-PMMA-beads were implanted (+ 160 mg gentamicin i.v. preop.) in a woman aged 73 years and with severely impaired kidney function. Frequent determination of gentamicin plasma concentrations and renal functions were possible. The plasma concentration reached a plateau at approx. 3 micrograms/ml. No accumulation of gentamicin in plasma occurred.
The purpose of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in... more The purpose of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in 10 male patients after injection of a high dose (731 mg) of racemic R,S-mepivacaine for a combined psoas compartment/sciatic nerve block. Arterial blood samples were taken, and the plasma concentrations of the stereoisomers R(+)and S(-)-mepivacaine were measured by means of high-performance liquid chromatography (HPLC) with a Qliral AGP column. The S(-) isomer reached higher plasma concentrations than the R(+) isomer. The maximal plasma concentration (G) of R(+) was 1.54 2 0.34 pg/mL, whereas that of the S(-) isomer was 2.34 * 0.51 p@mL (P = O.OOO50). The time at which C, , was reached (T-J was identical for both isomers, The area under the plasma concentration-time m e from t = 0 to infinity (AUCm) of S(-)-mepivacaine was almost double that of R(+)-mepivacaine. The elimination half-life (Tm) was identical for both isomers (3 h), which means that the calculated total body clearance and the calculated steady-state volume of the distribution of R(+) are, respectively, 1.7 and 1.5 times larger than that of the S(-) isomer. We conclude that the plasma concentrations of the S(-)mepivacaine isomer were higher than those of the R(+) isomer because of a smaller volume of distribution and a slower total body clearance. (Anesth Analg 1992,7575-80) epivacaine is a racemic mixture of R(+)-and S(-)-mepivacaine, with the S(-) the more (5). The aim of this study was to investigate the pharmacokinetics of R(+)-and S(-)-mepivacaine in 10 patients Accepkd for publication
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