Zidovudine, lamivudine, and nelfinavir concentrations in amniotic fluid and maternal serum.
OBJECTIVE
The objective of this study was to examine lamivudine (3TC), zidovudine (ZDV), nelfinavir (NFV), and its active nelfinavir metabolite (M8) concentrations in paired maternal plasma and amniotic fluid samples to determine antiretroviral penetration or accumulation in the fetal compartment.


METHODS
Ten paired amniotic fluid and maternal plasma samples were obtained during caesarian section for pharmacokinetic analysis. Antiretroviral concentrations were measured in both matrices using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS) methodologies.


RESULTS
Median maternal plasma concentrations for NFV, M8, 3TC, and ZDV were 456, 244, 176, and 794 ng/mL, respectively, while median amniotic fluid concentrations were 118, 21, 2537, and 1483 ng/mL, respectively. The median NFV amniotic fluid to maternal plasma ratio was 0.44; the median M8 ratio was 0.11. Median 3TC and ZDV amniotic fluid to plasma ratios were 11.9 and 1.5, respectively.


CONCLUSIONS
NFV and M8 exhibited partial drug transfer and/or accumulation in the amniotic compartment, whereas ZDV and 3TC concentrations mostly exceeded that in maternal plasma. Overall, all drugs achieved exposures in the amniotic fluid in excess of their wild-type viral susceptibilities. Amniotic fluid is an important compartment in the prevention of mother-to-child transmission; a further understanding of protease inhibitor and other antiretroviral drug penetration into amniotic fluid is warranted.
Division of Clinical Pharmacology, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294-0019, USA.
Chantelle
C
Bennetto-Hood
Yvonne J
YJ
Bryson
Alice
A
Stek
Jennifer R
JR
King
Mark
M
Mirochnick
Edward P
EP
Acosta
D000653:Amniotic Fluid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013058:Mass Spectrometry; D019888:Nelfinavir / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood / Q000188:drug therapy*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D017320:HIV Protease Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019888:Nelfinavir