| Abstract | The population pharmacokinetics of atovaquone were examined in 458 black, Oriental, and Malay patients with acute Plasmodium falciparum malaria receiving atovaquone alone or concomitantly with other drugs. Oral clearance (CL/F) showed a 0.674 power relationship with weight and is similar in Oriental and Malay subjects but 58.5% lower in black subjects. On the basis of mean body weight, the population estimate of CL/F is 3.28, 8.49, and 9.13 L/hr in black, Oriental, and Malay subjects, respectively. The relationship between apparent volume of distribution (V area/F) and weight was linear and similar in all three races at 7.98 L/kg. The population estimate of V area/F is 345, 383, and 428 L in black, Oriental, and Malay subjects, respectively. The bioavailability of the high and low doses of atovaquone was similar. Neither CL/F nor V area/F were significantly affected by age, gender, and the coadministration with chloroguanide (proguanil), pyrimethamine, and tetracycline. Half-life (t1/2) showed a 0.326 power relationship with weight; thus, the population estimate of t1/2 in black, Oriental, and Malay subjects is 72.9, 31.3, and 32.5 hours, respectively. The final magnitudes of interpatient variability in CL/F and V area/F were 68% and 49%, respectively. |
| Authors | Z Hussein, J Eaves, D B Hutchinson, C J Canfield
(Affiliation: Glaxo Wellcome, Beckenham, and Pharmaceutical Systems Inc., Talent, Oregon, USA.)
|
| Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 61
Issue 5
Pg. 518-30
(May 1997)
ISSN: 0009-9236 UNITED STATES |
| PMID | 9164414
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antimalarials
- Naphthoquinones
- Atovaquone
|
| Topics |
- Adolescent
- Adult
- Analysis of Variance
- Antimalarials
(blood, pharmacokinetics, therapeutic use)
- Atovaquone
- Child
- Child, Preschool
- Computer Simulation
- Databases, Factual
- Dose-Response Relationship, Drug
- Female
- Gabon
- Humans
- Kenya
- Malaria, Falciparum
(blood, drug therapy, metabolism)
- Male
- Middle Aged
- Models, Biological
- Naphthoquinones
(blood, pharmacokinetics, therapeutic use)
- Philippines
- Thailand
- Zambia
|
