Prodrugs pharmacokinetics

Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y. A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans the mechanism for tumor-selective accumulation of 5-FU. Pharm Res 2001 Aug 18(8) 1190-202. 

Dopamine, a vasodilator, has been widely used for treatment of acute circulatory failure. However, since dopamine is rapidly metabolized when administered orally, its use has been limited to intravenous infusion. Murata et al., studied the bioavailability and the pharmacokinetics of orally administered dopamine (DA). The oral administration of DA to dogs resulted in an absolute bioavailability of approximately 3%. To minimize the extensive first-pass metabolism of DA, a dopamine prodrug, V-(/V-acetyl-l-mcLhionyl)-o,o-bis(cLhoxycarbonyl)dopamine (TA-870), was synthesized [28] (Fig. 6). Since DA is a substrate for both mono-... 

In conclusion, CPD represents a prodrug of captopril which seems to lengthen the pharmacokinetic half-life and extend the duration of action of captopril in humans. 

A Garzon, A Poupaert, M Claesen, P Dumont. A lymphotropic prodrug of L-dopa Synthesis, pharmacological properties, and pharmacokinetic behavior of 1,3-dihex-adecanoyl-2-r(S)-2-amino-3-(3,4-dihydroxyphenyl) propanoyl] propane-1,2,3-triol. J Med Chem 29 687-691, 1986. 

S Ehrnebo, O Nilsson, LO Boreus. Pharmacokinetics of ampicillin and its prodrugs bacampicillin and pivampicillin in man. J Pharm Biopharmacokin 7(5) 429-451, 1979. 

K Murata, N Kazuo, K Kohano, MJ Sanejirna. Bioavailability and pharmacokinetics of an oral dopamine prodrug in dogs. J Pharm Sci 78(10) 812-814,... 

U Klotz. Clinical pharmacokinetics of sulfasalazine, its metaboliters and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokin 10 285-302, 1985. 

BG Petty, RI Whitty, S Liao, HC Krasny, LE Rocco, LG Davis, PS Lietman. Pharmacokinetics and tolerance of desciclovir, a prodrug of acyclovir, in healthy human volunteers. Antimicrob Agents Chemother 31 1317-1322, 1987. 

Weller, S., Blum, M. R., Doucette, M., Burnette, T., Cederberg, D. M., de Miranda, P., Smiley, M. L., Pharmacokinetics of the acyclovir prodrug valaciclovir after escalating single- and multiple-dose administration to normal volunteers, Clin. Pharmacol. Ther. 1993, 54, 595-605. 

Wire MB, Shelton MJ, Studenberg S (2006) Fosamprenavir Clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 45 137-168. 

Careful prodrug design is required to minimize the number of proposed candidates and maximize the explored space of physicochemical and pharmacokinetic properties. The ability to predict target properties (e.g., solubility, extent of absorption, and rate of activation) is a major need in rational prodrug design, but global quantitative models simply do not exist, despite... 

B. Testa, J. M. Mayer, Concepts in Prodrug Design to Overcome Pharmacokinetic Problems , in Pharmacokinetic Optimization in Drug Research Biological, Physicochemical, and Computational Strategies , Eds. B. Testa, H. van de Waterbeemd, G. Folk-ers, R. Guy, Verlag Helvetica Chimica Acta, Zurich, 2001, p. 85-95. 

N. L. Pochopin, W. N. Charman, V. J. Stella, Pharmacokinetics of Dapsone and Amino Acid Prodrugs of Dapsone , Drug Metab. Dispos. 1994, 22, 770-777 N. L. Pochopin, W. N. Charman, V. J. Stella, Amino Acid Derivatives of Dapsone as Water-Soluble Prodrugs , Int. J. Pharm. 1995, 121, 157-167. 

In an attempt to improve the pharmacokinetic properties of hybrid triglyceride prodrugs, a number of hybrid pseudolipid analogues were prepared with the glyceryl moiety replaced by a 1,3-diaminopropyl moiety. As... 

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