Tolerance and pharmacokinetics of propacetamol, a paracetamol formulation for intravenous use

Abstract

In 12 healthy volunteers, paracetamol pharmacokinetics were compared following administration of 1 g propacetamol HCl given intravenously over a 15-min period and 500 mg paracetamol given orally. Mean +/- SD total AUC (microgram/ml.h) following the iv formulation was significantly (P < 0.01) greater than following oral paracetamol (25.53 +/- 4.27 vs 21.04 +/- 4.49) corresponding to a mean oral bioavailability of paracetamol of 82.2 +/- 9.4%. Between 1 and 2 h after administration, paracetamol plasma concentrations became very similar following both formulations. In another study, 2 g propacetamol HCl was given both as a 15-min infusion and as a 2-min bolus injection to six healthy volunteers. Contrary to mild to moderate local discomfort experienced during the 2-min bolus injection, the 15-min infusion was well tolerated without any complaints reported.

The Evaluation of Safety and Analgesic Efficacy of Paracetamol and Ibuprofen Followed by Impacted Third Molar Surgery

“…Prodrug of paracetamol that can be administered parenterally when greater efficacy or a fast onset of analgesia is desirable. IV infusion of propacetamol 2 g was significantly more effective than paracetamol 1 g taken orally in patients with moderate to severe postoperative pain after hallux valgus surgery (13,14). There are conflicting results concerning preemptive and preventive administration of different groups of analgesics.…”

Influence of Medium and Temperature on the Hydrolysis Kinetics of Propacetamol Hydrochloride: Determination Using Derivative Spectrophotometry

“…At these times, the reduction obtained for the pH values of the solutions was of approximately 1 pH unit, which is worth considering because the pH of the solution is important in local intolerance to parenteral administration. Despite the low pH of the solutions, Depré et al 8) reported that the local and systemic tolerability of 1 g and 2 g of PRO given intravenously was excellent.…”

“…[10][11][12][13] In these circumstances, PRO can be administered in physiologic or glucose solutions since it is rapidly and quantitatively hydrolyzed into PA by plasma estearases within 7 min after intravenous injection. 8) With the exception of absorption, PRO exhibits similar disposition kinetics when given by either the intravenous route as PA or by mouth as conventional tablets. 14) Screening of the literature revealed that PRO can be analytically determined by first-derivative spectrophotometry.…”

“…7) Due to its poor water solubility that prevents parenteral administration in a soluble form, the clinical indications for PA are limited, especially in the postoperative setting. Contrary to the latter, propacetamol hydrochloride [N-N-diethyl, 4-acetylamino) phenyl ester monohydrochloride] (PRO) is a water-soluble prodrug of paracetamol, which can be parenterally administered as analgesic 8,9) for the treatment of postoperative pain, acute trauma, and gastric and/or intestinal disorders where oral administration is not possible. PRO has also shown efficacy in the symptomatic control of fever in the fields of oncology, infectious disease, and hematology.…”

Green approach for drug design and discovery of paracetamol analogues as potential analgesic and antipyretic agents

“…The pharmacological effects in clinical trials have shown that 2 possesses efficacy similar to that of 1. However, due to its greater water solubility, it can be parenterally administered and thus be employed when oral administration is not possible (5). Phthalimide derivatives have been widely reported to possess beneficial pharmaceutical effects, like analgesic (7), antiinflammatory (8) and antiviral (9) activities.…”