Human intravenous pharmacokinetics and absolute oral bioavailability of cefatrizine
| Autor: | M Pfeffer, J Ximenez, R C Gaver |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
Adult
Male Administration Oral Biological Availability Absorption (skin) Pharmacology Pharmacokinetics Oral administration medicine Humans Infusions Parenteral Pharmacology (medical) Antibacterial agent Volume of distribution Cefatrizine Chemistry Blood Proteins Middle Aged Crossover study Cephalosporins Bioavailability Kinetics Infectious Diseases Protein Binding Research Article medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 24:915-920 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.24.6.915 |
| Popis: | Cefatrizine was administered intravenously and orally at dose levels of 250, 500, and 1,000 mg to normal male volunteers in a crossover study. Intravenous pharmacokinetics were dose linear over this range; mean peak plasma concentrations at the end of 30-min infusions were, respectively, 18, 37, and 75 micrograms/ml, total body clearance was 218 ml/min per 1.73 m2, renal clearance was 176 ml/min per 1.73 m2, and mean retention time in the body was 1.11 h. Cumulative urinary excretion of intact cefatrizine was 80% of the dose, and half-lives ranged from 1 to 1.4 h. Steady-state volume of distribution was 0.22 liters/kg. On oral administration, the absolute bioavailabilities of cefatrizine were 75% at 250 and 500 mg and 50% at 1,000 mg. The mean peak plasma concentrations and peak times were, respectively, 4.9, 8.6, and 10.2 micrograms/ml at 1.4, 1.6, and 2.0 h, mean residence times were 2.4, 2.6, and 3.1 h, and mean absorption times were 1.3, 1.6, and 1.9 h. Oral renal clearance and half-life values corresponded well to the intravenous values. Cumulative urinary excretion of intact cefatrizine (as percentage of dose) was 60 at 250 mg, 56 at 500 mg, and 42 at 1,000 mg. It is hypothesized that the lack of oral dose linearity between the 500- and 1,000-mg doses is due to a component of cefatrizine absorption by a saturable transport process. Relative absorption at the high dose would be sufficiently slow that an absorption "window" would be passed before maximum bioavailability could be attained. It is not expected that the observed bioavailability decrease at doses exceeding 500 mg will have any therapeutic significance, since clinical studies are establishing efficacy for a recommended unit dosage regimen of 500 mg. |
| Databáze: | OpenAIRE |
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