Pharmacokinetics of contraceptive steroids in patients with cystic fibrosis.

Abstract

The pharmacokinetics of the commonly used contraceptive steroids ethinyloestradiol and levonorgestrel were investigated after oral and intravenous administration in six women with cystic fibrosis.The results were compared with data obtained from healthy women of similar age. The total body clearance of ethinyloestradiol was significantly higher in the patients with cystic fibrosis (0 61 (SD 0-19) 1/h/kg) than in control women (0-32 (0 16) 1/h/kg; p < 002). In addition, the oral bioavailability of ethinyloestradiol was greater in women with cystic fibrosis than in controls (76-9% (11 7%) compared with 47 3% (7-5%); p < 0-001). As a result of these two changes, the area under the plasma concentration-time curve after an oral dose of ethinyloestradiol was similar in patients and controls. The pharmacokinetics of levonorgestrel did not differ significantly between patients with cystic fibrosis and healthy women. The data suggest that women with cystic fibrosis will receive similar contraceptive protection from these steroids as do healthy women.

Pregnancy and cystic fibrosis: Approach to contemporary management

“…barrier method). Limited pharmacokinetic studies in CF support the use of standard dose of the oral contraceptive pill, 49 though similar to the general population they should not be prescribed in patients with a prior history of venous thrombosis, significant CF-related liver disease or pulmonary hypertension.…”

Contraceptive safety among women with cystic fibrosis: a systematic review

“…Studies report that CF patients have lower serum levels of many orally administered drugs compared to healthy controls, likely attributable to enhanced drug clearance and possibly decreased rates of absorption [15]. Nonetheless, we identified one pharmacokinetic study that suggests that the absorption of ethinyl estradiol and levonorgestrel is not impaired in women with CF and that CF patients achieve the same plasma concentrations as healthy controls, suggesting that they will receive similar contraceptive protection from COCs [11]. However, this study was small and it is not known the extent to which these findings can be extrapolated to other COC preparations or delivery systems.…”

“…After reviewing the titles and abstracts of these articles, as well as the full articles when necessary, six articles met our inclusion criteria [8][9][10][11][12][13] and an additional article was identified examining contraceptive use among women, most with CF, after undergoing lung transplantation [14] (Table 1). Of the seven included articles, four examined measures of disease severity or other CF-related health outcomes and four, including one that also examined disease severity, examined measures of effectiveness (three reported on pregnancies and one was a pharmacokinetic study).…”

“…Finally, a pharmacokinetic study examined six female CF patients aged 20-30 years and six healthy women of similar age who were randomly assigned to receive to receive 50 μg ethinyl estradiol and 250 mcg levonorgestrel orally or intravenously; the study was repeated with the participants receiving the alternate route of administration four or more days later [11]. Blood samples were taken at predetermined intervals up to 24 h post-administration to examine plasma ethinyl estradiol and levonorgestrel concentrations and the area under the plasma concentration-time curve from 0 to 24 h (AUC 0-24 ).…”

Contraception and pregnancy in cystic fibrosis

“…These studies suggest that women with CF using oral contraception are likely to receive a similar contraceptive effect as do healthy women. 11 Careful monitoring remains important however in view of the possible changes in clinical status and treatment regimens, such as the use of new antibiotics. The interaction of antibiotics and the OCP is often a concern in CF.…”