Bioavailability of paracetamol, phenylephrine hydrochloride and guaifenesin in a fixed-combination syrup versus an oral reference product

Abstract

Objectives: The primary objective of this study was to compare the bioavailability of paracetamol, phenylephrine hydrochoride and guaifenesin in a new oral syrup with an established oral reference product. The secondary objective was to compare the safety of the new syrup and the reference product.Methods: This was a single-centre, open-label, randomized, reference-replicated, crossover study. Healthy adult volunteers received one dose of syrup and two separate doses of a reference oral liquid formulation in a randomized sequence over three study periods, with a washout interval of !7 days between study periods. Blood samples were taken regularly postdose and analysed for paracetamol, phenylephrine hydrochoride and guaifenesin concentrations; adverse events were recorded. Results: This study enrolled 45 subjects. For paracetamol and guaifenesin, the syrup and reference product were considered to be bioequivalent. Bioequivalence was not shown for phenylephrine hydrochoride. All adverse events were mild or moderate, most of which were considered formulation related. Conclusions: The syrup did not reach bioequivalence with the reference product, as bioequivalence could not be shown for phenylephrine hydrochoride. This may be due to differences in the excipients between the two products. Both the syrup and the reference product had a good safety profile and were well tolerated.

Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

“…When the results from this study are compared to those previously reported for adults, good agreement is generally observed. In children, peak plasma concentrations occurred at 0.5 hour, which is similar to that reported in adults (0.25 to 0.7 hour) . The t 1/2,z in children increased with age (0.6 to 1 hours) but was similar to that reported in adults (0.8 to 1.0 hours) .…”

“…In children, peak plasma concentrations occurred at 0.5 hour, which is similar to that reported in adults (0.25 to 0.7 hour). 2,11,12 The t 1/2,z in children increased with age (0.6 to 1 hours) but was similar to that reported in adults (0.8 to 1.0 hours). 2,11,12 In addition, dose-adjusted systemic exposure in adolescents 12 to 17 years of age was also similar to adults (adolescents following 400 mg: C max = 2316 ng/mL, AUC = 4062 ng · h/mL; adults following 600 mg: C max = 3177 ng/mL, AUC = 4905 ng · h/mL (ie, dose-adjusted C max and AUC were 8% and 19% lower in adults, respectively).…”

Novel Stereoselective High‐Performance Liquid Chromatographic Method for Simultaneous Determination of Guaifenesin and Ketorolac Enantiomers in Human Plasma

“…Following the coadministration of GUA and KET, plasma levels of the drugs' enantiomers were measured using the described methodology. After 1.5 h of drugs administration, GUA levels were found to be 263 ng/mL ( S (+) GUA), 240 ng/mL ( R (–) GUA), which are reasonably consistent with previously reported data, based on total GUA levels . Since no previous study dealt with measuring the individual GUA enantiomers in human plasma, this study is considered novel in this respect.…”

“…After 1.5 h of drugs administration, GUA levels were found to be 263 ng/mL (S (+) GUA), 240 ng/mL (R(-) GUA), which are reasonably consistent with previously reported data, based on total GUA levels. 42,43 Since no previous study dealt with measuring the individual GUA enantiomers in human plasma, this study is considered novel in this respect. However, plasma levels found for KET were as follows: 480 ng/mL for R (+) KET and 180 ng/mL for S (-) KET, which are slightly higher compared with those reported for KET monotherapy.…”

Synthesis and Antiepileptic Activity Evaluation of Valproic Acid Derivatives by Niche Chemistry

“…Valproic acid (1.58 mL, 0.01 mol) and acetaminophen (tylenol) (1.51 g, 0.01 mol) were dissolved in 20 mL of THF in a 250 mL one necked round‐bottomed flask thoroughly dried at room temperature using a Deanstark apparatus after stirring for 24 h. The water removed by esterfication reaction was confirmed, and the degree and completion of the reaction were confirmed by TLC. The resulting sticky oil was purified by flash column chromatography (eluent; EA: n‐hexane = 2: 8 v/v) (Figure ).…”