Pharmacokinetics of cefotiam in humans

Abstract

After intravenous bolus injections of 0.5, 1, and 2 g of cefotiam to three healthy volunteers, the mean (± standard deviation) total plasma clearances measured for each dose were, respectively, 26.8 ± 2.7, 22.8 ± 0.8, and 17.8 ± 0.9 liters/h; the terminal elimination half-lives were 54.0 ± 0.1, 68 ± 15, and 98 ± 36 min; and the renal clearances were 16.0 ± 2.9, 13.3 ± 1.4, and 11.3 ± 2.6 liters/h. The 24-h urinary recovery was independent of the dose and averaged 53% of the dose. After intramuscular administration of 1 g of cefotiam to three healthy volunteers, a mean (± standard deviation) peak concentration of 16.6 ± 5.1 ,ug/ml was reached at 0.75 to 1 h post dosing. The concurrent intramuscular administration of lidocaine and cefotiam did not modify the kinetics of cefotiam. During a constant-rate infusion, the steady-state plasma clearance decreased slightly when the infusion rate was increased. There was no trend towards accumulation of cefotiam in plasma during chronic treatment with 1 g intravenously every 12 h for 10 days.Cefotiam (Halospor; Ciba-Geigy) is a new injectable cephalosporin with a broad spectrum of activity against grampositive and gram-negative bacteria (5, 6). The pharmacokinetics of cefotiam have been reported to be dose dependent in normal volunteers after intravenous infusions (15 to 60 min) of doses ranging from 0.5 to 2 g (1). In patients with various degrees of renal impairment, a good correlation has been found between the renal clearance of cefotiam and the creatinine clearance (4). A dosage adjustment was proposed.The present study was designed to determine the pharmacokinetic properties of'cefotiam in humans after single bolus administration by the intravenous and intramuscular routes. The effect of the dose was investigated in the range of 0.5 to 2 g after bolus intravenous administration. Since lidocaine may be added to cefotiam when it is given intramuscularly, the effect of its concurrent administration on the pharmacokinetics of cefotiam was examined. To measure eventual variation of the plasma clearance of cefotiam with the concentration of cefotiam in plasma, the steady-state plasma clearance was measured during two successive intravenous infusions at different rates. The pharmacokinetics were also investigated in patients given repeated doses intravenously. The following four treatment regimens were applied. (i) Regimen 1. Three healthy volunteers were given 0.5, 1, and 2 g of cefotiam intravenously in a Latin square design. These doses were dissolved in 3, 6, or 12 ml of sterile water and injected over 1 min. Intervals of 1 week separated administration of the three doses. Blood samples were collected before the injection and at 0, 2, 5, 10, 20, and 30, min and 1, 1.5, 2, 3, 4, 5, 6, and 8 h after injection. Urine was collected before administration and at 0 to 1, 1 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 10, and 10 to 24 h postinjection. MATERIALS AND METHODS(ii) Regimen 2. Three healthy volunteers received 1 g of cefotiam alone intravenously (10 ml) and 1 g of cefotiam intr...

Antibiotic Prophylaxis in Cerebrospinal Fluid Shunting: Reassessment of Cefotiam Penetration into Human CSF

“…This has been confi rmed for ventricular and cisternal caverns as well as for variable latency periods after maximum concentrations of Cefotiam in blood. The pharmacokinetic parameters describing the C / t profi les of Cefotiam in plasma agreed well with previously published data [6,29] . Short-term infusions of standard prophylactic doses of 2 g Cefotiam yield plasma levels exceeding the MIC 90 of relevant pathogens.…”

“…Therapeutic doses of 2 g Cefotiam i.v. resulted in blood concentrations of 132.6 ± 21.7 mg / L and 34.3 ± 6.2 mg / L 30 and 60 min after the end of the application, respectively [29] . The concentration in parotid saliva reached 9.5 ± 3.4 mg / L after 30 min [25] , in homogenates of soft tissue from the neck 8.6 ± 3.5 mg / g after 90 min [23] .…”

“…The pharmacokinetics of Cefotiam in blood after intravenous administration is similar to that of other cephalosporins. Selected properties of Cefotiam [6,29] [18] . The antibacterial activity of ß -lactams such as Cefotiam depends on the time span over which the " free " concentration, i.e.…”

Cefotiam disposition in markedly obese athlete patients, Japanese sumo wrestlers

“…Other likely reasons may include an increased renal blood flow secondary to the changes in blood volume and cardiac output due to the increase in body weight of obese subjects (2,13). Since about 50 to 70% of the cefotiam is excreted unchanged in urine (11,16,17), the larger CL of cefotiam found in the sumo wrestler group is probably attributable to enhanced renal function.…”

Biliary Excretion of Antimicrobial Drugs

“…Approximately 50% of the administered dose is excreted in the urine as an active unchanged drug [71]. Biliary excretion varies considerably among different species.…”