Intravenous Paracetamol as an Antipyretic and Analgesic Medication: the Significance of Drug Metabolism

Abstract

Abstract.One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measurements of core temperature and of pain intensity were done for 6 h. Additional rescue medications were recorded for 5 days. Blood was sampled for the measurement of free paracetamol (APAP) and of glucuronide-APAP and N-sulfate-APAP by an HPLC assay. Defervescence, defined as core temperature below or equal to 37.1°C, was achieved in 52 patients (73.2%) within a median time of 3 h. Patients failing to become afebrile with the first dose of paracetamol became afebrile when administered other agents as rescue medications. Analgesia was achieved in 25 patients (86.4%) within a median time of 2 h. Serum levels of glucuronide-APAP were greater among non-responders to paracetamol. The presented results suggest that the intravenous formulation of paracetamol is clinically effective depending on drug metabolism.

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

“…It should be noted that one original finding described by our group in a previous open‐label trial was validated here. In our previous study , 1 g paracetamol was administered intravenously for the management of fever and pain in 100 patients. Pharmacokinetic analysis showed that concentrations of the glucuronide‐APAP metabolite were greater in the serum of patients who failed to experience relief of their symptoms.…”

“…Collected blood samples were centrifuged and serum was stored at –70°C. After thawing, concentrations of free paracetamol (APAP), glucuronide‐APAP and N‐sulfate‐APAP were measured after analysis through a high‐performance liquid chromatography system by an assay developed in‐house, as described elsewhere .…”

“…It was anticipated that, in each centre, defervescence would be achieved in 10% of patients allocated to the placebo arm. If the true within‐centre odds ratio for achievement of defervescence in the paracetamol group relative to the placebo group was 7, based on a previous publication , then the study required 40 subjects in each group to be able to reject the null hypothesis that this odds ratio equals 1, with a probability (power) of 0.9. The Type I error probability associated with this test of the null hypothesis is 0.05 using a continuity‐corrected Mantel–Haenszel chi‐squared statistic.…”

“…These patients were administered 1 g paracetamol intravenously within 15 min. Defervescence was achieved in 73.2% of patients within 3 h .…”

“…These studies found intravenous paracetamol to have a rapid antipyretic effect . The only available publication on the antipyretic effect of intravenous paracetamol in infections described a population of 71 Greek patients enrolled in a prospective, open‐label, single arm trial . These patients were administered 1 g paracetamol intravenously within 15 min.…”