Chronopharmacokinetic Studies of Pranoprofen and Procainamide

Abstract

There is increasing evidence demonstrating that plasma drug concentrations are affected by their time of administration. In the current study, the chronopharmacokinetic profiles of an antipyretic agent, pranoprofen, and an antiarrhythmic agent, procainamide, were examined. In the first study, 75 mg of pranoprofen was given orally in seven healthy subjects at 10:00 (morning trial) or 22:00 (evening trial). In the second study, 500 mg of procainamide was given orally in eight subjects with premature ventricular contractions at 10:00 or 22:00. Blood samples for plasma drug concentrations were taken for a 10-hour (pranoprofen study) or a 24-hour (procainamide study) post-drug period. In the first (pranoprofen) study, the mean time to maximum concentration was significantly shorter, and the mean maximum plasma concentration as well as absorption rate constant had a tendency to be greater after the morning than after the evening trial. The mean area under the plasma concentration-time curve, elimination half-life or oral clearance of the morning and evening dosages did not differ. In the second (procainamide) study, no significant difference was observed in any pharmacokinetic parameter concerning procainamide or its active metabolite, N-acetyl-procainamide (NAPA) between the morning and evening trials. These data indicate that plasma levels of pranoprofen are affected by its administration time while plasma concentrations of procainamide and NAPA do not vary with the time of dosage.

Chronopharmacology of enalapril in hypertensive patients

“…This corresponds to a shorter t .... and a greater Cm~x during the day. Such time-dependent phenomena have not been observed with hydrophilic agents [11][12][13].…”

“…For example, lipohilic agents are absorbed more rapidly after administration during the daytime than in the night in humans [11][12][13]. This corresponds to a shorter t .... and a greater Cm~x during the day.…”

Determination of nonsteroidal anti-inflammatory drugs in human plasma by LC-MS-MS with a hydrophilic polymer column

“…Intraday preci- Table 3 Regression equations, limits of detection (LOD), and limits of quantitation (LOQ) for six NSAIDs in human plasma using the present method a Data given as mean ± SD calibration are summarized in Table 6. These concentrations in plasma were within therapeutic levels [22,[30][31][32][33][34].…”

“…The LOD values of all drugs under optimal conditions were 0.002-0.005 μg/ml; the LOQ values were 0.01-0.02 μg/ml. The therapeutic levels of NSAIDs were reported to be 16.1 μg/ml for alminoprofen [30], 11.3 μg/ml for zaltoprofen [22], 15.3-53 μg/ml for tiaprofenic acid [31], 4.45 μg/ml for pranoprofen [32], 17-49 μg/ml for ibuprofen [33], and 8.2-14.6 μg/ml for fl urbiprofen [34]. Therefore, our present method is sensitive enough to analyze their therapeutic levels.…”

Chronopharmacokinetics

“…The antiarrhythmic drugs cibenzoline (cifenline) [Brazzell et al 1985] and procainamide (Fujimura et al 1989) displayed no significant variations in their pharmacokinetics in relation to time of administration (table III). However, it was not investigated whether administration of these drugs at different times ofthe day caused any variation in their pharmacological effect.…”