Disposition, pharmacokinetics

Absorption/Distribution - Propafenone is nearly completely absorbed after oral administration with peak plasma levels occurring approximately 3.5 hours after administration. It exhibits extensive first-pass metabolism resulting in a dose-dependent and dosage-form-dependent absolute bioavailability. Propafenone follows a nonlinear pharmacokinetic disposition presumably due to saturation of first-pass hepatic metabolism as the liver is exposed to higher concentrations of propafenone and shows a very high degree of interindividual variability. 

Metabolism/Excretion - There are 2 genetically determined patterns of propafenone metabolism. In more than 90% of patients, the drug is rapidly and extensively metabolized with an elimination half-life of 2 to 10 hours. These patients metabolize propafenone into two active metabolites 5-hydroxypropafenone and N-depropylpropafenone. They both are usually present in concentrations less than 20% of propafenone. The saturable hydroxylation pathway is responsible for the nonlinear pharmacokinetic disposition. 

Watts DH, Brown ZA, Tartaglione T, Burchett SK, et al. 1991. Pharmacokinetic disposition of zidovudine during pregnancy. J Infect Dis. 163 226-232. 

The pharmacokinetic dispositions of other stilbenes that are structurally similar to resveratrol and have pharmacological activity across many anticancer, anti-inflammatory, and antioxidant assays have been studied. The pharmacokinetics was characterized in male Sprague-Dawley rats after single intravenous... 

Takino, T., Nagahama., E., Sakaeda, T., Yamashita, F., Takakura, Y., and Hashida, M. (1995) Pharmacokinetics disposition analysis of lipophlic drugs injected with various lipid carriers in the single-pass rat liver perfusion systerrlnt. J. Pharm., 114 43-54. 

Shin, B.S., et al. 2004. Nasal absorption and pharmacokinetic disposition of salmon calcitonin modified with low molecular weight polyethylene glycol. Chem Pharm Bull 52 957. 

Table 3.5 Pharmacokinetic disposition parameters of therapeutic monoclonal antibodies.

Studies have shown that PCP causes adverse effects to the liver, kidneys, blood, lungs, CNS, immune system, and gastrointestinal tract both after a short-or long-term exposure.60,61 Direct contact with PCP causes irritation to the skin, eyes, and mouth, particularly when it is a hot vapor. In view of its importance during earlier years, extensive studies of Braun and associates61 63 demonstrated the metabolism and pharmacokinetic disposition of PCP in rats, nonhuman primates, and humans. All these studies indicated the adverse effects of PCP to animals and humans.59-67... 

Blythe L L, Craig A M, Christensen J M et al 1986 Pharmacokinetic disposition of dimethyl sulfoxide administered intravenously to horses. American Journal of Veterinary Research 47 1739-1743 Bottoms G D, Fessler J F, Roesel O F et al 1981 Endotoxin-induced hemodynamic changes in ponies effects of flunixin meglumine. American Journal of Veterinary Research 42 1514-1518... 

Norman W M, Court M H, Greenblatt D J 1997 Age-related changes In the pharmacokinetic disposition of diazepam in foals. American Journal of Veterinary Research 58 878-880... 

American Journal of Veterinary Research 61 1579-1586 Nolan A, Reid J, Welsh E et al 1996 Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine a pharmacokinetic study. Research in Veterinary Science 60 262-266 Norman W M, Court M H, Greenblatt D J 1997 Age-related changes in the pharmacokinetic disposition of diazepam in foals. American Journal of Veterinary Research 58 878-880... 

Hennessy, D.R., Sangster, N.C., Steel, J.W. Collins, G.H. (1993) Comparative pharmacokinetic disposition of closantel in sheep and goats. Journal of Veterinary Pharmacology and Therapeutics, 16, 254-260. 

Ali, D.N. Hennessy, D.R. (1996) The effect of level of feed intake on the pharmacokinetic disposition and efficacy of ivermectin in sheep. Journal of Veterinary Pharmacology and Therapeutics, 19, 89-94. 

The dose of warfarin is patient-specihc, based on the desired intensity of anticoagulation and the patient s individual response. There is tremendous interpatient variabhity with regard to the pharmacodynamic response and pharmacokinetic disposition of warfarin. 

During pregnancy, not only is the fetus at risk for drug teratogenicity (see Chap. 76), but also the pharmacokinetic disposition of certain drugs may be altered. Penicillins, cephalosporins, and aminoglyco-... 

Kalman, D. Barriere, S.L. Johnson, B.L., Jr. Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid. Antimicrob.Agents Chemother., 1992, 36, 453-457... 

Pharmacokinetic (dispositional or Pharmacodynamic Learned tolerance Behavioral Conditioned Acute tolerance Reverse tolerance (sensitization) Cross-tolerance metabolic)... 

Venlafaxine does not alter the pharmacokinetic disposition of alcohol in healthy volunteers. 

Barriere SL, Cathn DH, Orlando PL, Noe A, Frost RW. Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of aziocillin. Antimicrob Agents Chemother (1990) 34,823-6. 

Gin AS, Stringer KA, Welage LS, Wilton JH, Matthews GE. The effect ofverapamil on the pharmacokinetic disposition of theophylline in cigarette smokers. J Clin Pharmacol (1989) 29, 728-32. 

Whatever the mechanism, a pharmaceutical incompatibility between sodium heparin and chlorpromazine hydrochloride solutions is confirmed. The clinical significance of an interaction between the two drugs after administration has not been demonstrated. The type of electrode reaction demonstrated in the model in vitro system may occur in vivo, because a biological membrane has been shown to be capable of acting as an electrode and it known that heparin is taken up by cell membranes. Binding of chlorpromazine to other mucopolysaccharides may be of significance in the pharmacokinetic disposition of the drug. 

Waldmeier, F. Flesch, G. Mlhler, P. Winkler, T. Kriemler, H.-P. Buhlmayer, P. de Gasparo, M. Pharmacokinetics, disposition and biotransformation of [ C]-radiolabehed valsartan in healthy male volunteers after a single oral dose, Xenobiotica, 1997,27, 59-71. 

Structure activity relationships between physicochemical properties of a drug and its pharmacokinetic disposition have been investigated. 

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