title: Pharmacokinetics of pentoxifylline and its main metabolites in patients with different degrees of heart failure following a single dose of a modified-release formulation.
abstract: Pentoxifylline (PTX) is extensively metabolized in the body, and all its 3 plasma metabolites (M1, M4, M5) are pharmacologically active. The authors evaluated the pharmacokinetics of PTX and its metabolites in 20 patients with chronic heart failure (CHF). Eleven had moderate and 9 severe CHF. The time courses of PTX, M1, M4, and M5 plasma levels were determined after oral administration of a sustained-release 600-mg tablet of PTX, and for each compound, AUC, maximal plasma concentration (C(max)), and time to C(max) (T(peak)) were calculated. Compared with patients with moderate CHF, those with severe CHF showed a significant delay in T(peak) of PTX (3.9 vs 1.6 hours) and M5 (5.6 vs 3.6 hours), a 59% significant increase in M5 AUC, and a 56% nonsignificant increase in PTX AUC. In the whole population, the AUCs of PTX, M4, and M5 were inversely correlated with markers of liver function, whereas the AUCs of M4 and M5 were inversely correlated with the creatinine clearance. In view of the kinetic features of slow-release formulations (flip-flop phenomenon), the delay in T(peak) of PTX in patients with severe CHF compared with moderate CHF should be ascribed to a reduced elimination rate.
authors: Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.
authors: Alessandra
authors: A
authors: Nisi
authors: Marco
authors: M
authors: Panfili
authors: Giovanni
authors: G
authors: De Rosa
authors: Giovanni
authors: G
authors: Boffa
authors: Francesca
authors: F
authors: Groppa
authors: Milena
authors: M
authors: Gusella
authors: Roberto
authors: R
authors: Padrini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline