Pharmacokinetics of 2-fluorodideoxycytidine (2FddC) in patients infected with human immunodeficiency virus.
Br J Clin Pharmacol
; 35(3): 255-60, 1993 Mar.
Article
em En
| MEDLINE
| ID: mdl-8385974
ABSTRACT
1. The aim of this study was to estimate an oral dosage regimen of 2FddC giving peak plasma drug concentrations close to the antiretroviral IC50 of 150 ng ml-1. 2. A total of 55 doses (40 intravenous infusions and 15 oral solutions) were given to 21 patients. One group (n = 6-11) received single doses of 0.01 mg kg-1 intravenously (i.v.), 0.1 mg kg-1 i.v. and 0.1 mg kg-1 orally (p.o.) in that order. The other group (n = 8-10) received single doses of 0.03 mg kg-1 i.v., 0.3 mg kg-1 i.v. and 0.3 mg kg-1 p.o. in that order. Blood and urine samples were collected up to 24 h after each dose for drug assay by h.p.l.c.-u.v. 3. The peak plasma concentrations of 2FddC were proportional to dosage across the range 0.03 to 0.3 mg kg-1. After intravenous dosing, the mean (%CV) volume of distribution was 60 (28) 1 and the mean (CV%) plasma clearance was 23 (23) 1 h-1. On average, 71% of the dose was recovered unchanged in urine and renal clearance exceeded concurrent creatinine clearance. 4. Plasma concentrations reached mean peaks of 37 and 96 ng ml-1 after oral doses of 0.1 and 0.3 mg kg-1, respectively. The mean absolute bioavailability was 50% within a 95% confidence interval of 20 to 80%. 5. The adverse events were usually mild or moderate in severity and were generally attributed to the disease rather than the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Infecções por HIV
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Síndrome da Imunodeficiência Adquirida
/
Zalcitabina
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Br J Clin Pharmacol
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Reino Unido