Theobromine metabolism and pharmacokinetics in pregnant and nonpregnant Sprague-Dawley rats |
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Authors: | Carol A. Shively Stanley M. Tarka |
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Affiliation: | Life Sciences Research, Hershey Foods Corporate Technical Center, Hershey, Pennsylvania 17033 USA |
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Abstract: | The plasma kinetics of po administered theobromine (TBR) were determined in timed-pregnant (P) and nonpregnant (NP) Sprague-Dawley rats at doses of 5, 10, 50, and 100 mg/kg using TBR sodium acetate with 10 μCi [8-14C]TBR as a radioactive tracer. Since plasma radioactivity consisted of >99% TBR and <1% metabolites as shown by high-performance liquid chromatographic (HPLC) methods, liquid scintillation counting was used to quantify plasma TBR. No dose-dependent kinetics were observed in mean TBR plasma half-life, volume of distribution, systemic clearance, area under the curve-dose normalized, or time to reach maximum plasma concentration in either P or NP rats. The kinetic parameters of P rats were strikingly similar to NP rats at all TBR dosage levels employed. Analysis of urinary metabolites by HPLC and a radioactivity monitoring system after a single po TBR dose of 5 and 100 mg/kg with 10 μCi [8-14C]TBR revealed similar qualitative metabolic patterns in P and NP rats. Compounds identified in the urine were TBR (39 to 62%), 6-amino-5-[N-methylformylamino]-1-methyluracil (20 to 32%), 3-methylxanthine and 7-methylxanthine (8 to 15%), 3,7-dimethyluric acid (5 to 10%), and 7-methyluric acid (5 to 7%). |
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Keywords: | Address all correspondence to: Stanley M. Tarka Jr. Ph.D. Hershey Foods Corporate Technical Center 1025 Reese Avenue Hershey Pa. 17033. |
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