Pharmacokinetics of levonorgestrel in the rat

Contraception (Impact Factor: 2.34). 08/1984; 30(1):81-8. DOI: 10.1016/0010-7824(84)90081-7
Source: PubMed


Levonorgestrel was administered intravenously as a bolus to adult female rats and blood samples were collected at various time intervals. Serum concentrations of levonorgestrel were measured by radioimmunoassay. Analysis of data for two- and three-compartment open models indicated that in the rat, as in the human and the rabbit, a tri-exponential equation provided a better fit of the data. The half-lives for the alpha, beta and gamma phases were 10.1 min, 42.7 min and 23.1 hours, respectively. These values were closer to those reported for women than were the half-lives reported for the rabbit. The alpha and the beta phases appeared to last for 51 min and 1.3 hours, respectively, and the gamma phase was longer than 45 hours.

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    ABSTRACT: Adult female rats were given a single, subcutaneous injection of 8, 16 or 32 micrograms of levonorgestrel (LNG). Blood samples were collected at various time intervals and serum concentrations of LNG were determined by radioimmunoassay. The patterns of temporal decline in LNG concentrations in the three dose groups indicated that the pharmacokinetics of LNG during the post-absorptive, rapid-elimination (beta) phase in the rat may be dose-dependent. Half-life, Co and AUC increased with the dose and -beta decreased as the dose increased. Mathematical relationships have been presented which can be used to predict the four parameters as well as concentrations of LNG at any given time after subcutaneous administration during the beta-phase for a given dose in the range of 8-32 micrograms. Significance of dose-dependent pharmacokinetic studies is discussed.
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    ABSTRACT: Rapid, sensitive, selective and accurate LC/MS/MS method was developed for quantitative determination of levonorgestrel (LNG) in rat plasma and further validated for specificity, linearity, accuracy, precision, sensitivity, matrix effect, recovery efficiency and stability. Liquid-liquid extraction procedure using hexane:ethyl acetate mixture at 80:20 v:v ratio was employed to efficiently extract LNG from rat plasma. Reversed phase Luna column C18(2) (50×2.0mm i.d., 3μM) installed on a AB SCIEX Triple Quad™ 4500 LC/MS/MS system was used to perform chromatographic separation. LNG was identified within 2min with high specificity. Linear calibration curve was drawn within 0.5-50ng·mL(-1) concentration range. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency at three quality control (QC) concentrations 0.5 (low), 5 (medium) and 50 (high) ng·mL(-1) was found to be >90%. Stability of LNG at various stages of experiment including storage, extraction and analysis was evaluated using QC samples, and the results showed that LNG was stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of LNG in rats after SubQ injection, providing its applicability in relevant preclinical studies.
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