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.
(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.
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.
(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.
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