Pharmacokinetics of oral zidovudine administered during labour: a preliminary study.
OBJECTIVE
The aim of this study was to determine whether oral zidovudine (ZDV) given during labour would provide a similar systemic exposure to the established intravenous regimen used to prevent mother-to-child transmission in HIV-infected pregnant women.


METHODS
ZDV pharmacokinetic parameters following oral administration during labour were determined in 10 HIV-infected pregnant women in active labour. All subjects were converted to intravenous ZDV prior to delivery.


RESULTS
In cohort 1 (n=6), subjects received 300 mg oral ZDV every 3 h for three doses. Oral therapy was well tolerated but plasma ZDV concentrations were substantially lower than previously reported with continuous intravenous therapy. Based on the pharmacokinetic results from cohort 1, women in cohort 2 (n=4) received an initial 600 mg dose followed by two 400 mg doses every 3 h. ZDV area under the curve and concentrations in cohort 2 increased approximately in proportion to the increase in dose but varied 6-7-fold. In both cohorts, ZDV pharmacokinetic parameters suggested erratic absorption.


CONCLUSIONS
While ZDV exposure improved with the increased dosing regimen, our sample size was small and larger studies are needed to establish whether oral ZDV administration during labour can consistently provide equivalent exposure to intravenous administration.
Mirochnick
M
M
Department of Pediatrics, Boston University School of Medicine, Boston, MA 02118, and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN, USA. markm@bu.edu
Rodman
J H
JH
Robbins
B L
BL
Fridland
A
A
Gandía
J
J
Hitti
J
J
Bardeguez
A
A
Rathore
M H
MH
Gonzalez Garcia
A
A
Cababasay
M
M
Samson
P
P
Mofenson
L
L
Bryson
Y J
YJ
Dorenbaum
A
A
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000284:Administration, Oral; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007743:Labor, Obstetric / Q000187:drug effects; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D015215:Zidovudine