Pozniak A, Yoganathan K, McNicol S, Dixon R, Posner J, Rolan P; International Conference on AIDS.
Int Conf AIDS. 1993 Jun 6-11; 9: 501 (abstract no. PO-B30-2196).
Dept. of Genitourinary Medicine, King's College Hospital, Beckenham, Kent.
OBJECTIVES: Atovaquone (566C80; 2-hydroxy-3-trans-4'-(4-chlorophenyl)cyclohexyl-1,4-naphthoquinone) is a potent selective inhibitor of pyrimidine synthesis in protozoa and has clinical activity against Pneumocystis, Toxoplasma and Plasmodia. Bioavailability in man using the existing tablet formulation is low and not dose-proportional due to low aqueous solubility, with slow and irregular absorption, and is lower in AIDS patients than in healthy volunteers. We have examined the rate and extent of absorption of a suspension of atovaquone. METHODS: HIV positive patients (non-AIDS) with CD4 counts < 200 cells/microliters were studied. Single dose sequence: Six patients received oral doses of 500mg, 1000mg and 1500mg at weekly intervals after an overnight fast. Plasma samples were taken at intervals for 2 weeks and analysed by HPLC. Multiple dose sequence: Six patients received 1000mg twice a day for 14 days. Trough samples were taken during drug dosing and for 14 days afterwards. RESULTS: Single dose sequence: Mean (SD) AUCs following; 500mg was 210 (91); 1000mg was 341 (85); 1500mg was 272 (56) micrograms/ml.h. Mean C maxs were: 3.2 (2.5); 6.2 (1.6) and 5.3 (1.1) micrograms/ml and Median T maxs 2.7 (1.0); 1.5 (0.5); 1.8 (0.8) hrs respectively. Multiple dose sequence: The mean (range) steady state concentration was 28.5 (13.5-52.5) micrograms/ml. CONCLUSIONS: With this formulation adequate plasma levels can be achieved with twice daily doses, without the requirement for food.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Antigens, CD4
- Area Under Curve
- Atovaquone
- Biological Availability
- Food
- Food-Drug Interactions
- HIV Seropositivity
- Humans
- Male
- Naphthoquinones
- Pneumonia, Pneumocystis
- Single Person
- Solubility
- immunology
Other ID:
UI: 102205199
From Meeting Abstracts