An oral fixed combination of ibuprofen and N-acetylcysteine as granules for oral solution. A drug-drug interaction study

Research Article

Abstract

Introduction: The common cold and other upper respiratory tract infections, although self-limiting, are highly prevalent and can be debilitating. Over-the-counter medications such as analgesics, antipyretics and mucolytics are widely used in all population groups for symptomatic treatment of acute upper respiratory tract infections, especially when associated with pain, fever, and cough. A new pharmaceutical form containing a combination between an analgesic and a mucolytic has been developed. The objective of this study was to assess if a drug-drug interaction (DDI) exists in terms of relative bioavailability of an oral fixed combination of 400 mg ibuprofen and 200 mg N-acetylcysteine (NAC) compared to two market standards, containing the two components separately.

Methods: An open, randomized, single dose, three-period, crossover trial in 24 healthy volunteers was conducted. Subjects were randomly assigned to receive either 1 sachet of granules for oral solution (400 mg ibuprofen + 200 mg NAC – Test product) or 1 sachet of granules for oral solution (400 mg ibuprofen – Reference 1) or 1 effervescent tablet (200 mg NAC – Reference 2) on three single occasions under fasting conditions. To investigate the DDI in terms of relative bioavailability of the products, the 90% confidence intervals were calculated for the ratios Test vs. Reference 1 and Test vs. Reference 2 of the pharmacokinetic endpoints AUC(0-t) and C_max of ibuprofen and NAC and then compared to the corresponding acceptance ranges. Safety and tolerability were assessed during the entire duration of the study.

Results: No relevant pharmacokinetic interaction between ibuprofen and NAC formulated as fixed combination was detected. All the three medications (Test, References 1 and 2) were similarly well tolerated and did not show any relevant differences regarding safety.

Conclusions: A new oral fixed combination of ibuprofen and NAC as granules for oral solution was developed. No drug- drug interaction in term of relative bioavailability between the two drug substances was detected.