Factors Responsible for the Variability of Saquinavir Absorption: Studies Using an Instrumented Dog Model
| Autor: | Soheir Tawfik, Yun K. Tam, Hugh Wiltshire, Nuzhat Tam-Zaman |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
viruses
Pharmacology toxicology Administration Oral Biological Availability Pharmaceutical Science Absorption (skin) Pharmacology Dog model Dogs Animals Medicine Pharmacology (medical) Saquinavir business.industry digestive oral and skin physiology Organic Chemistry biochemical phenomena metabolism and nutrition Bioavailability Kinetics Intestinal Absorption Liver Molecular Medicine business Biotechnology medicine.drug |
| Zdroj: | Pharmaceutical Research. 21:436-442 |
| ISSN: | 0724-8741 |
| DOI: | 10.1023/b:pham.0000019296.47762.3f |
| Popis: | To study the effect of dose and food on the bioavailability of saquinavir in dogs.A Youden Square block design was used for six female mongrel dogs (20-24 kg) who received six saquinavir treatments. The six randomized treatments were 1 mg/kg intravenous infusion over 30 min; 200, 400, 600, and 800 mg of saquinavir in the form of 200-mg capsules given orally with food; and 400 mg of saquinavir given orally after an overnight fast. A 200-mg 14C-saquinavir capsule was used to replace one of the 200-mg unlabeled saquinavir capsules in the 200- and 800-mg oral study.Absorption of saquinavir from the gut was variable. (F(A): 49-95%). The 14C-saquinavir study shows that the total radioactivity absorbed from the gut was insignificantly different from that of unlabeled saquinavir, suggesting first-pass gut metabolism was unimportant. The bioavailability of saquinavir under fasting condition was significantly lower (8.41 +/- 4.7% vs. 20.3 +/- 2.6%, p0.05). Saquinavir underwent significant first-pass liver metabolism because hepatic clearance values (22 to 30 ml min(-1) kg(-1)) approached that of liver blood flow.Incomplete gut absorption and extensive first-pass liver metabolism are the causes for low bioavailability of saquinavir in dogs. Absorption was further reduced under fasted conditions. |
| Databáze: | OpenAIRE |
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