Pentoxifylline

Oral pentoxifylline (PTX) is almost completely absorbed but has low bioavailability of 20-30% due to extensive first-pass metabolism; three of the seven known metabolites, M1, M4, and M5 are present in plasma and appear soon after dosing.A226560, A226565, L30300 Single oral doses of 100, 200, and 400 mg of pentoxifylline in healthy males produced a mean t_max of 0.29-0.41 h, a mean C_max of 272-1607 ng/mL, and a mean AUC_0-? of 193-1229 ng\*h/mL; corresponding ranges for metabolites 1, 4, and 5 were 0.72-1.15, 114-2753, and 189-7057.^A226545 Single administration of a 400 mg extended-release tablet resulted in a heightened t_max of 2.08 ± 1.16 h, lowered C_max of 55.33 ± 22.04 ng/mL, and a comparable AUC_0-t of 516 ± 165 ng\*h/mL; all these parameters were increased in cirrhotic patients.^A226550 Smoking was associated with a decrease in the C_max and AUC_steady-state of metabolite M1 but did not dramatically affect the pharmacokinetic parameters of pentoxifylline or other measured metabolites.^A226555 Renal impairment increases the mean C_max, AUC, and ratio to parent compound AUC of metabolites M4 and M5, but has no significant effect on PTX or M1 pharmacokinetics.^A226560 Finally, similar to cirrhotic patients, the C_max and t_max of PTX and its metabolites are increased in patients with varying degrees of chronic heart failure.^A226565 Overall, metabolites M1 and M5 exhibit plasma concentrations roughly five and eight times greater than PTX, respectively. PTX and M1 pharmacokinetics are approximately dose-dependent, while those of M5 are not. Food intake before PTX ingestion delays time to peak plasma concentrations but not overall absorption. Extended-release forms of PTX extend the t_max to between two and four hours but also serves to ameliorate peaks and troughs in plasma concentration over time.^L30300