Pharmacokinetics and Safety of Ketorolac Following Single Intranasal and Intramuscular Administration in Healthy Volunteers

Abstract

Ketorolac was administered to 15 healthy volunteers in a phase 1, single-dose, crossover, randomized study. Subjects received open-label randomized 15- and 30-mg intramuscular (i.m.) ketorolac and blinded randomized 15- and 30-mg intranasal (i.n.) ketorolac. The i.n. ketorolac was well tolerated; the only nasal symptoms were some instances of mild irritation. The i.n. ketorolac was rapidly and well absorbed (median tmax, 0.50-0.75 hours), and the half-life was approximately 5 to 6 hours, values that were similar to those following i.m. administration. Relative bioavailability of i.n. compared to i.m. administration at the same doses was approximately 67% to 75%. Dose proportionality was noted between the 15- and 30-mg i.n. and i.m. dose levels. Thus, i.n. ketorolac offers a therapeutic alternative to i.m. administration and may provide benefits in the clinical setting.

Sensitization of central trigeminovascular neurons: Blockade by intravenous naproxen infusion

“…Allodynic patients from our earlier study (Jakubowski et al, 2005) who were rendered painfree using parenteral ketorolac -the only intravenous formulation of NSAID currently approved in the US -testified that ingestion of oral NSAID formulations did nothing in the way of aborting their migraine attacks. Given that oral and intravenous administration of COX inhibitors result in similar profiles of plasma concentration (Jung et al, 1988, Pasloske et al, 1999, McAleer et al, 2007, and that intrathecal doses that block pain caused by peripheral inflammation are less than 100th of the doses required systemically (Malmberg and Yaksh, 1992), we suggest that non-parenteral administration somehow leads to sub-optimal concentration of NSAIDs in the dorsal horn. It may prove useful to investigate whether the eventual concentration attained in the dorsal horn using parenteral vs. non-parenteral NSAID formulations is related to their efficacy in aborting migraine with allodynia.…”

Analgesia with Low-Dose S(+)-ketamine in Laparoscopic Cholecystectomy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…Ketorolac, administered in its active form, has immediate bioavailability to inhibit cyclooxygenase (COX); it thus regulates the synthesis of prostaglandins and decreases the inflammatory cascade [15]. The analgesic power of ketorolac might have been enough for the adequate control of pain; the use of rescue analgesia was, therefore, unnecessary, and a possible analgesic effect of S(+)-ketamine could not observed.…”

Antimigraine drugs: new frontiers

“…In a phase I, single dose, five-way crossover, randomized study, absorption of ketorolac started immediately, and median t max ranged from 0.50 to 0.75 h postdose, irrespective of the dose of ketorolac [10]. There was a terminal phase half-life of approximately 5-6 h. Very similar profiles were observed for the IM doses.…”