Ethanol kinetics: extent of error in back extrapolation procedures.

1. Plasma ethanol concentrations were measured in 24 male volunteers for 9 h after a single oral dose of 710 mg kg-1. 2. The rate of decline of the plasma ethanol concentration (k0; mean +/- s.d.), was 186 +/- 26 mg l-1 h-1. 3. In each individual, three elimination rates were used to back-extrapolate plasma ethanol concentrations over 3 and 5 h periods from observed values at 4 h and 6 h post-dosing assuming zero-order kinetics. The extrapolated values were then compared with the observed concentrations. 4. Using the mean k0 values for the subjects the mean error in back extrapolation was small but highly variable. The variability in the error increased with the length of the extrapolation period. 5. When a k0 value of 150 mg l-1 h-1 (a value often cited as a population mean) was used for back extrapolation this resulted in significant under-estimation of actual values whereas the use of a k0 value of 238 mg l-1 h-1 (the highest value observed in the present study) resulted in significant over-estimation of actual values. 6. These results indicate that because the kinetics of ethanol are associated with substantial inter-subject variability the use of a single slope value to back calculate blood concentrations can give rise to considerable error.

Comparison of a Bayesian forecasting technique with a new method for estimating phenytoin dose requirements.

A simple, novel approach to phenytoin dose adjustment recently proposed by Wagner has been compared with an established Bayesian method. A data set comprising a minimum of two steady-state concentration/dose pairs from each of 43 adult epileptic patients was used. Prediction error analysis demonstrated that the two methods were equally precise but that the Wagner method tended to underpredict concentrations. The slope of the semilogarithmic relationship between concentration and dose was found to be 54% higher than originally reported by Wagner. It may therefore be necessary to adjust Wagner's equation for different patient populations before this method is used in routine clinical practice.