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Abstract
Misoprostol (Cytotec, Searle) is a prostaglandin E1 analogue widely used for off-label
indications such as induction of abortion and of labour. This is one of a series of
reviews of methods of cervical ripening and labour induction using standardised methodology.
Healthcare providers, consumers, researchers and policy makers are inundated with unmanageable amounts of information, including evidence from healthcare research. It has become impossible for all to have the time and resources to find, appraise and interpret this evidence and incorporate it into healthcare decisions. Cochrane Reviews respond to this challenge by identifying, appraising and synthesizing research-based evidence and presenting it in a standardized format, published in The Cochrane Library (www.thecochranelibrary.com).<p><i>The Cochrane Handbook for Systematic Reviews of Interventions</i> contains methodological guidance for the preparation and maintenance of Cochrane intervention reviews. Written in a clear and accessible format, it is the essential manual for all those preparing, maintaining and reading Cochrane reviews. Many of the principles and methods described here are appropriate for systematic reviews applied to other types of research and to systematic reviews of interventions undertaken by others. It is hoped therefore that this book will be invaluable to all those who want to understand the role of systematic reviews, critically appraise published reviews or perform reviews themselves.
To compare the pharmacokinetics of vaginal and oral administration of the prostaglandin E1 analogue, misoprostol. Twenty women received 400-micrograms doses of misoprostol either orally or as tablets placed in the vagina. Serum levels of principal metabolite, misoprostol acid, were measured at 7.5, 15, 30, 45, 60, 90, 120, and 240 minutes. The first ten women were pregnant and undergoing first-trimester abortions, and the last ten were not pregnant and had additional blood sampling at 360 minutes. We compared the pharmacokinetics of misoprostol acid after oral and vaginal administration. All 20 subjects completed the study. The maximum mean (+/- standard deviation [SD]) of misoprostol acid differed significantly between the oral and vaginal groups (277 +/- 124 compared with 165 +/d- 86 pg/mL, respectively; P = .03, analysis of variance), as did the mean +/- SD time to peak levels (34 +/- 17 compared with 80 +/- 27 minutes, respectively; P < .001) and areas under the misoprostol concentration versus time curve (mean +/- SD) up to 4 hours (n = 20,273.3 +/- 110.0 compared with 503.3 +/- 296.7 pg.hour/mL, respectively; P = .033) and up to 6 hours (n = 10, 300.0 +/- 103.3 compared with 956.7 +/- 541.7 pg.hour/mL, respectively; P = .029). The extent of absorption was highly variable among subjects in each group. There are significant differences in the pharmacokinetics of misoprostol administered by vaginal and oral routes that may explain the difference observed in clinical efficacy. Assuming that the pharmacologic effect of misoprostol is related to its concentration in the plasma, our observation of the prolonged serum concentrations in the vaginal group suggests that vaginal administration could be dosed at longer intervals than oral.
[1
]University of the Witwatersrand, University of Fort Hare, Eastern Cape Department
of Health; Department of Obstetrics and Gynaecology, East London Hospital Complex;
Frere and Cecilia Makiwane Hospitals Private Bag X 9047 East London Eastern Cape South
Africa 5200
[2
]World Health Organization; UNDP/UNFPA/WHO/World Bank Special Programme of Research,
Development and Research Training in Human Reproduction, Department of Reproductive
Health and Research; 20 Avenue Appia Geneva Switzerland 1211
[3
]5 Chemin de La Voie-Creuse Geneva Switzerland 1202
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