Effect of dose on the pharmacokinetics of levonorgestrel in the rat during the rapid elimination phase following subcutaneous administration.

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.