Abstract
In previous chlorpromazine pharmacokinetic studies a dramatic elevation in blood plasma levels of this drug was observed when taken in
combination with oral contraceptives. Different mechanisms have been postulated to explain this observation. The aim of the study was to
investigate whether oral contraceptives such as ethinyloestradiol and progesterone enhance the absorption of chlorpromazine by means of
inhibiting P-glycoprotein (P-gp) and if this effect is mainly due to ethinyloestradiol or progesterone or their combination. The Caco-2 cell line
was used as an in vitro model to study the effects of these compounds on the transport of chlorpromazine. Both apical to basolateral (AP-BL)
and basolateral to apical (BL-AP) transport studies were done on chlorpromazine in combination with different compounds.
Ethinyloestradiol enhanced the AP-BL cumulative transport of chlorpromazine by 11.5% compared to the control group, which was also
statistically significantly higher than the effect caused by progesterone (0.8%). A combination of these two steroidal hormones enhanced the
cumulative transport of chlorpromazine by only 2.0% compared to the control group. This indicates the possible existence of separate drugbinding
sites for these two hormones and chlorpromazine on P-gp. The drug-binding site (or receptor) for progesterone probably interacts
allosterically with the binding site for ethinyloestradiol and thereby decreasing its transport enhancing effects on chlorpromazine.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:tut/oai:encore.tut.ac.za:d1001955 |
| Date | 06 March 2003 |
| Creators | Brown, D, Goosen, TC, Chetty, M, Hamman, JH |
| Publisher | Elsevier |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Text |
| Format | |
| Rights | Elsevier |
| Relation | European Journal of Pharmaceutics and Biopharmaceutics |
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