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Effect of hypophysectomy on caffeine elimination in rats
Author(s) -
Bienvenu T.,
Pons G.,
Rey E.,
Richard MO,
D'Athis P.,
Olive G.
Publication year - 1990
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1990.tb00693.x
Subject(s) - chemistry , endocrinology , medicine , volume of distribution , hematocrit , saline , dehydration , caffeine , metabolism , urine , urine flow rate , pharmacokinetics , biochemistry
Summary— Two groups of 8‐week‐old Sprague‐Dawley male rats were used: 8 hypophysectomized (H[‐]), operated on day 0, treated by daily sc tetracosactid (ACTHs: 10 μg), and thyroxine (T4:5 μg/100g); 7 sham‐operated, treated by sc saline solution. ACTHs, T4, saline solution were administered on days 7–16. The animals received po caffeine (CAF) 4 mg/kg as citrate salt on day 15. Ten blood samples were drawn from the tail. Plasma CAF concentrations were determined by HPLC. CAF apparent clearance and apparent volume of distribution were lower in H(‐) rats than in controls: 0.281 ± 0.072 vs 0.455 ± 0.165 1/kg/h (‐38%; P <0.05) and 0.520 ± 0.239 vs 1.28 ± 0.266 1/kg (‐59%; P <0.01) respectively. CAF half‐life was lower in H(‐) rats than in controls: 1.33 ± 0.621 vs 2.12 ± 0.676 h (‐37%; P <0.01). CAF is a drug with a low hepatic extraction ratio and low plasma protein binding. CAF clearance is therefore primarily dependent on intrinsic clearance, which depends on the activity of the enzymes involved in CAF metabolism. These data suggest that hepatic CAF metabolism is reduced in H(‐) rats treated by SC ACTHs and T4. The decrease in CAF apparent volume of distribution is probably related to dehydration, as suggested by increase in urine flow and hematocrit. The CAF half‐life was probably low because the volume of distribution was proportionally more decreased than the clearance. Our results suggest that the pituitary gland plays a role in the regulation of hepatic CAF metabolizing enzymes.