Pharmacokinetics of progesterone in laying and non-laying hens (Gallus domesticus)

The metabolic clearance rate (MCR), volumes of distribution (V(d)), production rate (PR) and half-life (t( 1/2 )) of progesterone were measured in laying hens 8 h before, during and 8 h after the preovulatory surge of progesterone, and in non-laying hens (pullets and moulting hens) after a single injection of [1,2,6,7-³H]progesterone. A curve-fitting computer program showed that the data of [³H]progesterone metabolism best fit a two-compartment model. The MCR of non-laying birds (163.2 ± 6.4 (S.E.M.) ml/min) was significantly greater than that of laying hens (122.4 ± 6.1 ml/min). The mean PR of progesterone in laying hens measured 8 h before and 8 h after the preovulatory peak of progesterone (42.498 ± 6.509 ng/min per kg^0.75) was comparable to that of moulting hens (61.771 ± 14.363 ng/min per kg^0.75). However, the PR of progesterone in hens when measured during the preovulatory surge of progesterone (254.335 ± 53.972 ng/min per kg^0.75) was significantly greater than 8 h before and 8 h after the surge. There were no significant differences among groups in the t( 1/2 ) of the distribution phase (combined mean, 1.03 ± 0.05 min), biologically active t( 1/2 ) (combined mean, 10.93 ± 0.31 min) or V(d) of the central compartment (V(d)A; combined mean, 609.4 ± 46.7 ml). However, the V(d) in the peripheral compartment (V(d)B) was significantly greater in non-laying birds (combined mean, 3891.3 ± 399.5 ml) compared with that of laying hens (combined mean, 2879.2 ± 154.4 ml). There was no significant difference for MCR (ml/min) and PR (ng/min) of progesterone for non-laying pullets between methods using a single injection or continuous infusion. However, when body weight differences between the two groups of pullets were taken into account and the values adjusted by covariance analysis, the MCR obtained with the continuous infusion method was significantly (P < 0.05) higher than the value obtained with the single injection method. It is concluded that (a) the preovulatory surge of progesterone is the result of an increase in the PR and not of a decrease in the MCR; (b) the lower MCR in laying hens compared with pullets and moulting hens is reflected by a smaller V(d)B, likely to be due to the presence of progesterone receptors of higher affinity and/or binding capacity in laying hens and to differences in extraction efficiency by progesterone-metabolizing organ systems; (c) t( 1/2 ) in the hen would appear to be shorter than that reported for mammalian species.