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Ketorolac (KT) is a potent analgesic drug effective in the treatment of moderate to severe pain. However, the scientific basis for KT prescribing are not clear. We have previously reported the indirect relationship between plasma levels (Cp) and analgesic effect (PK/PD) of KT in patients with severe pain. Notwithstanding, the ordered categorical nature of pain relief measurement and the delay of effect with respect to analgesic plasma concentration create problems in data interpretation and inference. This paper further reviews the PK/PD results applying a logistic univariate analysis to estimate the probability distribution of: (1) time to onset; (2) duration of effect and, importantly, (3) a certain degree of pain relief as a function KT concentration in the effect compartment (Ce). In addition, both the PD and logistic results were used to generate Cp, Ce and effect-time and analgesic effect-Ce curves for several doses of KT. Simulations would indicate that 10 mg dose elicits a greater onset time and a lesser duration time of effect than obtained with the readily administered 30 mg im dose of KT (60 and 330 min respectively). Otherwise, simulated 60 and 90 mg doses do not elicit significant advantage in onset time, although duration might be increased with regard to tested 30 mg dose of KT. However, the elevated Ce reached with such doses could be associated with side effects of this drug. Therefore, neither doses higher than 30 mg im of KT nor remedication before one hour should be considered adequate in the treatment of postoperative severe pain.
Usefulness of logistic-pharmacokinetic-pharmacodynamic analysis for rational dosing: The case of ketorolac in postoperative pain
Generically Dependent Continuant
Proceedings of the Western Pharmacology Society
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