Pharmacokinetics and pharmacodynamics of diprophylline
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Diprophylline is used in many countries as a bronchodilator. It is an N-substituted theophylline derivative which does not release theophyllinein vitro orin vivo. It therefore has its own pharmacokinetic and pharmacodynamic properties. In a cross-over study in ten healthy volunteers serum concentrations and urinary excretion were studied after administration of diprophylline.
Its serum decay after intravenous administration shows two-compartment kinetics with a rapid distribution. Theα-phase lasted on average 0.75 h andΒ was 0.427±0.118 h−1, corresponding with aΒ-phase half-life of 1.7±0.4 h. The mean volume of distribution was 0.70±0.20 l/kg, total body clearance 0.29±0.09 l.kg−1.h−1. About 84% of the drug is excreted unchanged in the urine. A comparison of the area under the curve suggests that the drug was almost completely absorbed from the gastro-intestinal tract. Its bioavailability is about 90%. Mean renal clearance values are higher than paired creatinine clearance values, which is an indication for active renal transport.
Peak levels of diprophylline were 7.4±2.2 mg/l at about 30 min after oral administration. The normal dose advocated is 200–400 mg three times a day. Inin vitro studies and in pharmacological animal studies diprophylline appears to be much less active than theophylline. Consequently estimated effective dosages are irrationally high.
KeywordsTheophylline Xanthine Renal Clearance Aminophylline Pharmaceutisch Weekblad Scientific Edition
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