Comparative bioavailability of two oral formulations of ketorolac tromethamine: Dolac^® and Exodol^®

Abstract

The bioavailability of ketorolac after administration of two oral formulations containing 10 mg of ketorolac tromethamine, Exodol and Dolac, to 12 healthy Mexican volunteers was compared. Subjects received both formulations according to a randomized crossover design and blood samples were drawn at selected times during 24 h. Ketorolac plasma concentrations were determined by HPLC and individual plasma-concentration-against-time curves were constructed. Maximal plasma concentration and AUC0-24 values were compared by analysis of variance followed by Westlake's confidence interval test. 90% confidence limits ranged from 80 to 125% for Cmax and from 85 to 118% for AUC0-24. It is concluded that the two assayed formulations are bioequivalent.

Determination of Racemic Ketorolac, Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV, Applied in Clinical Study During and After Pregnancy

“…Comparable satisfactory precision was shown in earlier studies for racemic ketorolac, e.g. CV <9 % [17,20], <5.3 % in plasma and <7.2 % in urine [16]. For ketorolac enantiomers, comparable precision was found by direct method [28] and higher CV % than found by other authors e.g.…”

“…linearity of calibration curves for plasma and for urine was found with calculated regressions as showed in Table 1. Wider linearity range for racemic ketorolac was observed in our method compared to earlier published methods [16][17][18]21]. a wider range of the calibration curve for ketorolac enantiomers (linearity up to 20 mg l −1 ) was observed earlier [25,26], but this is of minor clinical relevance in the measurement of low ketorolac enantiomers concentrations (up to 2.01 mg l −1 ) observed in our clinical plasma samples.…”

“…Wu et al [18] used threestage liquid-liquid extractions with diethyl ether and hexane for racemic ketorolac and p-hydroxy-ketorolac in plasma. Similar extraction was employed by other authors for racemic ketorolac in plasma [17,20]. For ketorolac enantiomers, indirect HPlC methods based on derivatization and using achiral HPlC were developed first [28][29][30].…”

“…So far, high performance liquid chromatography (HPlC) methods were described to determine racemic ketorolac in human plasma [16][17][18][19][20][21][22][23][24], racemic ketorolac in human urine [16,20,21], p-hydroxy-ketorolac in human plasma [18], p-hydroxy-ketorolac in human urine [20,21], ketorolac enantiomers in human plasma [20,22,[25][26][27][28][29] and ketorolac enantiomers in human urine [20]. Except for solid-phase extraction for racemic ketorolac [19,23,24] and for ketorolac enantiomers [22,29], published sample preparations include mainly liquid-liquid extractions for racemic ketorolac [17,18,20,21] and ketorolac enantiomers [20,[25][26][27][28]30]. Mroszczak et al [21] described ethyl acetate and hexane extraction Abstract In order to enhance the sensitivity and to develop a faster direct method for plasma and urine quantification of racemic ketorolac, its metabolites (p-hydroxyketorolac and ketorolac glucuronides) and ketorolac enantiomers, we developed an extraction procedure based on solid-phase extraction combined with specific and fast chromatographic separation.…”

Pharmacologic Properties of Ketorolac Tromethamine: A Potent Analgesic Drug

“…Such (7) have speculated that analgesia would be delayed with respect to plasma concentrations. The time to reach the maximal pain relief after ketorolac tromethamine administration is between 1 and 3 h (26,99), whereas the maximal plasma concentration is achieved in about 1 h (28,41,44).…”