Page 116 - 80 guidelines for the treatment of malaria_opt

nd
Guidelines for the treatment of malaria – 2 edition

• Tetracycline
A number of small studies have been conducted on tetracycline kinetics in malnourished
adults from India. One study compared the kinetics of intravenous and oral tetracycline in
malnourished and normal adult males (90). Compared to the control group, malnourished
patients had lower protein binding, shorter elimination half-life and reduced volume
of distribution. The authors suggest that in order to keep levels of tetracycline above
the minimum inhibitory concentration, the dose interval should be reduced. A similar
conclusion was reached by another study that also found more rapid distribution of
tetracycline and faster clearance in the malnourished group (91). The same author, in a
separate study, also looked at absorption of oral compared with intravenous tetracycline
in various types of malnutrition. Oral absorption was slower in patients with protein-
energy-malnutrition and pellagra than in patients with anaemia or vitamin B complex
deficiency patients and healthy controls. In a third study, patients with nutritional oedema
were found to have increased C max and area under the curve values, and reduced clearance
and volume of distribution compared with healthy controls (i.e. some differences with
non-oedema malnutrition patients) (92).
• Doxycycline
There is a single study examining the kinetics of doxycycline given orally to adult patients
in India (93). Area under the curve, elimination half-life and plasma protein binding were
reduced, and clearance increased in the malnourished group. Renal clearance was similar
in controls and malnourished patients. The authors surmised that increased total body
clearance of doxycycline might be due to higher metabolism in malnourished patients.
Steady state plasma C min levels were lower than in healthy patients but still within the
therapeutic range. A change in dose recommendation does not seem necessary given
these findings.

• Other antimalarials

There are no studies of the kinetics of clindamycin, amodiaquine, artemisinin derivatives
(dihydroartemisinin), artemether-lumefantrine, mefloquine or primaquine kinetics in
malnourished patients.

Conclusion

There are many reasons why pharmacokinetics may be different in malnourished
patients compared to those who are well nourished. However, with the possible
exception of quinine, there are insufficient data available for specific dosing changes to
be recommended.

102