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Abstract: Skandinavisk forum for reisemedisin. Copenhague mai 2002.

Do we use unnecessarily high does of mefloquine? A mathematic approach.

Gunnar Hasle, Reiseklinikken - Oslo Travel Clinic
Background: Adverse effects of mefloquine commonly results in reluctance to take the drug. As clinicians we often have to navigate between Scylla and Carybdis, in this case between the risk of prophylaxis failure and unacceptable, or even dangerous, side effects. Although the adverse effects of mefloquine shows an extreme individual variation, they are likely to be related to dose. It is therefore desirable to have a tool for calculating the amount of mefloquine retained after different dosis regimens. Theoretical considerations suggests that the doses recommended by WHO may be unnecessarily high. This presentation provides a simple mathematic model for calculating amounts of mefloquine retained in the body after different dosage regimens, as a help for designing optimal prophylaxis.

Methods: The general pharmacokinetic data on mefloquine were obtained from the manufacturers information. A general formula for retainment of a drug with first order kinetics is run in Microsoft Excel. For a drug with first order metabolization and individually varying half life, the theoretic amount of drug as a function of time will be:

An = (A0 + An-1)* 0,5t/h

An=amount retained at the time the new dose is taken. An-1 =amount retained one week earlier (before the previous dose was taken). A0=dose. t=time (days). h=half life (days).

Results, according to the model: With WHOs recommended dosage the amount of mefloquine may approach toxic levels in low weight individuals with slow metabolization of the drug. Even individuals with rapid excretion and metabolization of mefloquine should have sufficient levels of mefloquine in long term treatment with a weekly dosage of half the recommended dose. A full dose every second week will not give sufficient minimum concentrations.

Conclusion: Individuals who experience no adverse effects should use the dosage recommended by WHO. Individuals who have adverse effects after the second full dose, may continue the drug with half dose weekly. It should be sufficient to continue the drug for two weeks after leaving the malaria endemic area with full dose prophylaxis and for four weeks with half dose prophylaxis.

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