Bioavailability pharmacokinetics

Fig. 21.2. Reasons why the clinical development of drugs is sometimes terminated and the drug does not reach the market include safety issues, marketing reasons, lack of efficacy and/or pharmacokinetics/bioavail-...

Hepatic function impairment The pharmacokinetics, bioavailability and patient response to verapamil and nifedipine may be significantly affected by hepatic cirrhosis. 

Pharmacokinetics Bioavailability of tablet vs liquid is approximately 90%. Diphenoxylate is rapidly, extensively metabolized to diphenoxylic acid (difenoxine), the active major metabolite. Elimination half-life is approximately 12 to 14 hours. An average of 14% of drug and metabolites are excreted over 4 days in urine, 49% in feces. Urinary excretion of unmetabolized drug is less than 1% difenoxine plus its glucuronide conjugate constitutes approximately 6%. 

Mechanism of Action A nucleotide analog that inhibits HIV reverse transcriptase by being incorporated into viral DNA, resulting in DNA chain termination. Therapeutic Effect Slows HIV replication and reduces HIV RNA levels (viral load). Pharmacokinetics Bioavailability in fasted patients is approximately 25%. High-fat meals increase the bioavailability. Protein binding 0J%-12% Excreted in urine. Removed by hemodialysis. Half-life Unknown. 

Several LC-MS and LC-MS/MS methods were developed in plasma for only one antidepressant and, sometimes, its major metabolite(s) to perform pharmacokinetic, bioavailability, or bioequivalence studies. Analytical methods developed for these purposes require very low LLOQ values and, usually, narrow linear ranges covering the low range of the therapeutic concentrations are validated. In this context, several methodologies were described for the determination of fluoxetine [94, 95, 98-100], paroxetine [44, 71, 85, 101, 102], venlafaxine [48, 61, 64, 86, 103,104], sertraline [62, 68, 83], citalopram [46, 89] and escitalopram [105], mianserine [106, 107], mirtazapine [42], trazodone [84], nefazodone [51, 81], duloxetine [47, 50, 73], and bupropion [43], Deuterated analogues of the analyte of interest or of other drugs were employed by few authors as IS [43, 61, 73, 81, 85, 99] however, in most of these methods, another antidepressant or other therapeutic drug was used for this purpose. 

Somogyi A, Albrecht M, Kliems G, et al. (1981) Pharmacokinetics, bioavailability and EGG response of verapamil in patients with liver cirrhosis. Br J... 

A. Somogyi, M. Albrecht, G. Kliems, K. Schafter, and M. Eichelbaum, "Pharmacokinetics, bioavailability, and ECG response of verapamil in patients with liver cirrhosis," Br. ]. Clin. Pharmacol, 12 51-60 (1981). 

Button C, Gross D R, Johnston J T et al 1980 Digoxin pharmacokinetics, bioavailability, efficacy and dosage regimens in the horse. American Journal of Veterinary Research 41 1388-1395... 

Egorin, M.J. et al. (1996) Plasma pharmacokinetics, bioavailability, and tissue distribution in CDjF, mice of halomon, an antitumor halogenated monoterpene isolated from the red sAgaePortieriahornemanii. Cancer Chemother. Pharmacol. 39, 51-60... 

---