Hydroquinine pharmacokinetics after oral administration in adult patients with muscle cramps

Objective: This study was conducted to determine the pharmacokinetic proper ties of hydroquinine after oral administration in adult patients with muscl e cramps. The main reason for this study was the poor availability of pharm acokinetic data, hindering the design of studies to explore the possible re lationship between hydroquinine concentrations and effects. Methods: Sixteen adult patients with a clinical history of muscle cramps we re given once-daily oral doses of 300 mg hydroquinine hydrobromide for 4 da ys. Serum and saliva samples were taken following a predefined schedule unt il 24 h after the last dose. Urine was collected during the study period. H ydroquinine concentrations were measured, and calculations were made of pha rmacokinetic parameters using non-linear curve fitting. Results: Pharmacokinetics of hydroquinine could be best described using a o ne-compartment open model. After oral administration, hydroquinine was rapi dly absorbed (mean +/- SD: maximum concentration 2.43 +/- 0.68 mg/l; time t o maximum concentration 1.4 +/- 1.2 h; lag time 0.54 +/- 0.50 h). With an e limination half-life of 10.9 +/- 6.1 h, steady-state was reached in several days. The distribution volume was 1.24 +/- 0.29 l/kg, total clearance was 6.7 +/- 3.2 l/h. The measured unbound hydroquinine fraction was 8.6 +/- 3.0 %. No correlation was found between saliva and serum concentrations. Cumula tive urinary excretion of unchanged hydroquinine 24 h after the first dose was 35.5 +/- 9.2 mg. Conclusion: Pharmacokinetic properties of hydroquinine are roughly similar to those of quinine. The unchanged fraction of hydroquinine excreted in uri ne is higher than that reported for quinine. Saliva hydroquinine concentrat ions could not be related to serum values. Steady-state trough or other fix ed-time serum concentrations may prove useful for further optimisation of h ydroquinine dosage.