Hydroquinine pharmacokinetics after oral administration in adult patients with muscle cramps.

Objective: This study was conducted to determine the pharmacokinetic properties of hydroquinine after oral administration in adult patients with muscle cramps. The main reason for this study was the poor availability of pharmacokinetic data, hindering the design of studies to explore the possible relationship between hydroquinine concentrations and effects.

Methods: Sixteen adult patients with a clinical history of muscle cramps were given once-daily oral doses of 300 mg hydroquinine hydrobromide for 4 days. Serum and saliva samples were taken following a predefined schedule until 24 h after the last dose. Urine was collected during the study period. Hydroquinine concentrations were measured, and calculations were made of pharmacokinetic parameters using non-linear curve fitting.

Results: Pharmacokinetics of hydroquinine could be best described using a one-compartment open model. After oral administration, hydroquinine was rapidly absorbed (mean +/- SD: maximum concentration 2.43+/-0.68 mg/ 1; time to maximum concentration 1.4+/-1.2 h; lag time 0.54+/-0.50 h). With an elimination 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. Cumulative 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 urine is higher than that reported for quinine. Saliva hydroquinine concentrations could not be related to serum values. Steady-state trough or other fixed-time serum concentrations may prove useful for further optimisation of hydroquinine dosage.