Hum. Reprod. Advance Access originally published online on April 23, 2009
Human Reproduction 2009 24(8):1862-1869; doi:10.1093/humrep/dep108
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Pharmacokinetics of repeated doses of misoprostol
1 Department of Obstetrics and Gynaecology, The University of Hong Kong, 6/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China 2 Department of Pediatrics, Philipps University Marburg, Baldingerstrasse, 35043 Marburg, Germany
3 Correspondence address. E-mail: pcho{at}hkusua.hku.hk
BACKGROUND: Misoprostol is widely used in obstetrics and gynaecology for medical abortion, cervical priming and induction of labour. To aid the design of effective and safe regimens, we have investigated the pharmacokinetic parameters after the vaginal or sublingual administration of repeated doses of 400 µg of misoprostol.
METHODS: Women undergoing termination of pregnancy by suction evacuation were randomized to receive 400 µg of sublingual or vaginal misoprostol every 3 h for five doses. Venous blood was taken at 180, 200, 240, 360, 380, 420, 540, 560, 600, 720, 740, 780 and 900 min after the first dose of misoprostol for determination of the plasma level of misoprostol acid (MPA).
RESULTS: The peak plasma levels of MPA decreased with successive doses of vaginal misoprostol, whereas the peak plasma levels were similar with successive doses of sublingual misoprostol. After the third dose, the peak plasma levels of MPA after sublingual misoprostol were significantly higher than those after vaginal administration. After the final dose, the area under the MPA concentration–time curve after sublingual administration was significantly higher than that after vaginal misoprostol (P < 0.031). However, subgroup analysis in the vaginal administration group showed that the progressive decline in the peak plasma levels of MPA occurred only in women with significant vaginal bleeding.
CONCLUSIONS: The peak plasma level of MPA after each dose of misoprostol is higher and the bioavailability is also greater after sublingual administration, compared with that after vaginal administration, of repeated doses of misoprostol. The difference was probably due to the reduction in absorption of vaginal misoprostol in the presence of significant vaginal bleeding.
Key words: misoprostol/pharmacokinetics/sublingual/vaginal
Submitted on January 9, 2009; resubmitted on March 24, 2009; accepted on March 31, 2009.