Pharmacokinetics of temocillin after intravenous and intramuscular administration.

Pharmacokinetics of temocillin (BRL 17421) was studied in a crossover study in 10 male healthy volunteers after administration 1 g of temocillin intravenously or intramuscularly. The mean serum levels of temocillin at the 5th min after i.v. administration were 131.57 mg/ml, at 1 h 71.27 mg/l and at 12.12 mg/l. The values of the pharmacokinetic parameters were as follows: AUC 509.2 mg X h X l-1, t1/2 4.2 h-1, Vd ss 11.57 l, Vd area 12.28 l, CL 2049 ml X h-1. The urinary excretion by 12 h was 70.58% of the administered dose of temocillin. The mean serum levels of temocillin after i. m. administration were at 2 h 46.65 mg/l and at 12 h 15.89 mg/l, the corresponding pharmacokinetic parameters were: AUC 501.38 mg X h X l-1, t1/2 4.3 h-1, Vd 12.69 l. The urinary excretion by 12 h was 57% of the administered dose of temocillin. It follows from the study that pharmacokinetic parameters of temocillin after both ways of temocillin administration are very closed and that the dose 1 g of temocillin is sufficient to create effective serum levels for the majority of sensitive gramnegative organismus.

[Pharmacokinetics and dosage of mezlocillin administered by intravenous infusion]. / Beitrag zur Pharmakokinetik und Dosierung von Mezlocillin bei intravenöser Infusion.

Mezlocillin was administered to seven healthy adults by i. v. infusion at two different speeds. They received 1.6 g mezlocillin in five minutes with the initial loading infusion and 1.3 g mezlocillin in one hour with the following infusion. Our aim was to achieve a 100 mg/l steady state serum concentration. The mezlocillin concentrations in the serum averaged 118.7 (+/- 31.2) mg/l at the end of this infusion. Four hours later they were 2.79 (+/- 1.41) mg/l and after six hours 0.96 (+/- 0.93) mg/l. The urinary excretion during the six hours averaged 60.5% of the applied dose of 2.9 g mezlocillin. The pharmacokinetic parameters of mezlocillin were calculated automatically using a two-compartment model. The average values were the following: biological half-life (beta) 72.7 (+/- 26) minutes; total plasma clearance 2.447 (+/- 0.586) ml/s; distribution volume (Vd area) 15.30 (+/- 6.12) l, i. e. 0.21 l/kg. Deviations from the mezlocillin serum concentrations desired (100 mg/l) are explained by interindividual differences in the pharmacokinetic behaviour and by the use of a two-compartment model.

[Azlocillin--a new anti-pseudomonas penicillin. A review of the literature and pharmacokinetic studies]. / Azlocillin--Ein neues Anti-Pseudomonas-Penicillin. Literaturübersicht und eigene pharmakokinetische Untersuchungen.

We studied the pharmacokinetics of azlocillin in 11 healthy persons following an i. v. infusion of 5 g over 30 minutes. The azlocillin concentrations in serum and urine were measured microbiologically. The serum concentrations averaged 530.5 (+/- 79.2) mg/l at the end of the infusion and 9.4 (+/- 4.3) mg/l six hours later. 73.8% of the dose was excreted in the urine during a period of six hours. The serum concentrations of azlocillin were analysed using a two-compartment model, and the pharmacokinetic constants were calculated by a computer. The average biological half-life (beta-phase) of azlocillin was 70.2 (+/- 7.8) min, the plasma clearance was 1.869 (+/- 0.284) ml/sec and the distribution volume (Vd area) was 11.34 (+/- 2.05) l, i. e. 0.17 l/kg.

Interaction of tolbutamide and chloramphenicol in diabetic patients.

In study 1 we investigated 8 diabetic female patients treated with tolbutamide who received chloramphenicol to combat urinary tract infections. In 5 patients, chloramphenicol was found to produce a distinct decrease of glycemia. Evaluation of the whole series revealed that the latter averaged 31.5%. No patient developed a marked hypoglycemia. With one exception, the values of immunoreactive insulin (IRI) in serum were within normal. In study 2 we investigated another series of 8 diabetic patients. Given chloramphenicol, 7 patients registered an almost twofold increase in the mean morning tolbutamide level in serum and glycemia decreased by one fourth. No patient developed severe hypoglycemia. Tolbutamide increase in serum was not associated with a rise of IRI level in serum. All patients displayed steady chloramphenicol level in serum. Potential reasons for the development of hypoglycemia during the treatment with sulphonylurea antidiabetics are discussed.