Serum levels and pharmacokinetics of ordinary and sustained-release lithium carbonate in manic patients during chronic dosage

Abstract

Ordinary and sustained-release lithium carbonate were administered at approximately equivalent daily dosage (1.5 and 1.8 g = 20.2 and 24.3 mmol ordinary and sustained-release respectively) in a crossover fashion to 5 manic patients. Actual and theoretical steady state serum levels of both preparations were determined. The sustained-release preparation gave observed serum levels that differed widely from predicted levels. Despite larger inter and intra-subject variations the serum levels at commencement and end of the sampling period were fairly constant. The results suggest that the wide individual variations in steady state profiles may be a consequence of the effect of normal physiological variables on drug absorption in the patient/sickness/diet combination of this study. Apparent erratic absorption in some patients, especially with the sustained-release preparation, indicates that great caution should be exercised in deciding when to monitor serum levels as a guide to adjusting dose. A justification is presented for morning sampling time as the most appropriate, regardless of the type of formulation used.