Shortcut formulae for pharmacokinetic dosage adjustments.

Dosage adjustments can be difficult and time-consuming, especially for the non-specialist. The objective of this investigation was to obtain shortcut formulae to calculate dosage adjustments for (i) a drug obeying linear pharmacokinetics (i.e. first order) and given orally, by a continuous infusion or by an intermittent intravenous infusion; and (ii) a drug obeying Michaelis-Menten kinetics and given orally or by an intermittent intravenous infusion. Shortcut formulae are derived by assuming a steady-state model (e.g. one-compartment intermittent intravenous infusion) for a patient and drug and then dividing by the same equation, assuming a different dose and interval. The assumption underlying the division is that the patient's pharmacokinetic parameters do not change. The results obtained show that for drugs following linear pharmacokinetics and having the same dosage interval, the ratio of new dose : given dose is of course proportional to the ratio of desired steady-state concentration : measured steady-state concentration. If the interval is changed, then there are three variables: the dose, the steady-state concentration and the accumulation factor. The ratio of the doses is still proportional to the ratio of the steady-state concentrations but is also inversely proportional to the accumulation factors for the different dosage intervals. Furthermore, for intermittent infusions, the dosages calculated are equivalent to those obtained using the Sawchuk and Zaske method. With the shortcut formulae, it is more easily seen that most common dosage adjustments readily reduce to simple proportions or joint variation. These calculations can be quickly carried out with only the patient's terminal rate constant for linear pharmacokinetics and their Michaelis-Menten constant (Km) value for Michaelis-Menten kinetics. The methods are illustrated with actual patient examples.