Effects of drinking pattern on the peak/trough blood concentrations in drinking water studies

The effects of changes in drinking patterns on the expected peak/trough blood concentrations of test compounds were examined during rodent dosed drinking water studies. They were based on the assumption that the kinetics of the test compound is linear and time-invariant. Results indicate that drinking patterns have minor effects on the expected peak/trough concentrations and the time to reach these concentrations. If a 12-hr light/dark cycle starting at 7.00 is used for all the drinking patterns studied, the peak and trough concentrations will occur in the early morning and late afternoon, respectively. A comparison of the predicted versus experimentally determined pentachlorophenol (PCP) plasma concentrations in a 1-wk rat drinking water study revealed that using a circadian rhythm drinking pattern in the model generated the most satisfactory prediction. Predictions based on a square wave drinking pattern with 90% drinking activities in the night phase were also excellent. Triangular or sinusoidal drinking patterns were least accurate in predictions.