Placental transfer of ritonavir with zidovudine in the ex vivo placental perfusion model.
OBJECTIVE
The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine.


METHODS
Twelve placental perfusion studies were performed at trough (1-2 microg/mL) and peak (approximately 20 microg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined.


RESULTS
Transfer of ritonavir at trough concentrations was undetectable (<0.025 microg/mL). The clearance index of ritonavir at peak concentration was 0.085 +/- 0.05 and was unaffected by zidovudine. The fetal concentration of ritonavir was 0.0758 +/- 0.22 microg/mL at a maternal concentration of approximately 20 microg/mL and 25.5 +/- 6.9 microg/mL at a concentration of 100 microg/mL. There was no tissue accumulation of ritonavir either alone or with zidovudine.


CONCLUSIONS
The clearance index of ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of ritonavir.
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032, USA.
B M
BM
Casey
R E
RE
Bawdon
D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D006801:Humans; D008431:Maternal-Fetal Exchange; D009994:Osmolar Concentration; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D015203:Reproducibility of Results; D019438:Ritonavir / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D015215:Zidovudine; D019438:Ritonavir