Abstract

BackgroundParacetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. This study is conducted to investigate the relative bioavailability and bioequivalence between one fixed dose paracetamol/orphenadrine combination test preparation and one fixed dose paracetamol/orphenadrine combination reference preparation in healthy volunteers under fasted condition for marketing authorization in Malaysia.MethodThis is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2-period crossover study with a washout period of 7 days. Paracetamol/Orphenadrine tablets were administered after a 10-h fast. Blood samples for pharmacokinetic analysis were collected at scheduled time intervals prior to and up to 72 h after dosing. Blood samples were centrifuged, and separated plasma were kept frozen (− 15 °C to − 25 °C) until analysis. Plasma concentrations of orphenadrine and paracetamol were quantified using liquid-chromatography-tandem mass spectrometer using diphenhydramine as internal standard. The pharmacokinetic parameters AUC0-∞, AUC0-t and Cmax were determined using plasma concentration time profile for both preparations. Bioequivalence was assessed according to the ASEAN guideline acceptance criteria for bioequivalence which is the 90% confidence intervals of AUC0-∞, AUC0-t and Cmax ratio must be within the range of 80.00–125.00%.ResultsThere were 28 healthy subjects enrolled, and 27 subjects completed this trial. There were no significant differences observed between the AUC0-∞, AUC0-t and Cmax of both test and reference preparations in fasted condition. The 90% confidence intervals for the ratio of AUC0-t (100.92–111.27%), AUC0-∞ (96.94–108.08%) and Cmax (100.11–112.50%) for orphenadrine (n = 25); and AUC0-t (94.29–101.83%), AUC0-∞ (94.77–101.68%) and Cmax (87.12–101.20%) for paracetamol (n = 27) for test preparation over reference preparation were all within acceptable bioequivalence range of 80.00–125.00%.ConclusionThe test preparation is bioequivalent to the reference preparation and can be used interchangeably.Trial registrationNMRR- 17-1266-36,001; registered and approved on 12 September 2017.

Highlights

  • Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol

  • There were no significant differences observed between the AUC0-∞, AUC0-t and Maximum observed plasma concentration (Cmax) of both test and reference preparations in fasted condition

  • The clinical phase was conducted at Clinical Research Ward (CRW), Hospital Ampang; the bioanalysis was done at Bioavailability/ Bioequivalence (BA/BE) Laboratory, Attest Research Sdn Bhd and the statistical analysis was evaluated at Pharmacy-Attest Research Sdn

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Summary

Introduction

Paracetamol/Orphenadrine is a fixed dose combination containing 35 mg orphenadrine and 450 mg paracetamol. It has analgesic and muscle relaxant properties and is widely available as generics. One of the most well-known and commonly used analgesics in the world is paracetamol. Paracetamol can be used alone or as an adjunct with other drugs to produce a synergistic effect. One of these drugs is orphenadrine, where it is used to provide an added analgesic effect in addition to muscle relaxant in the treatment of painful muscle spasms

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