E-DRUG: Paediatric drug formulations (cont'd)
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I agree with Beverley, the efficacy of the orally administered drug is dependent on the drug properties as well as on the patient factors. The drug related factors such molecular weight, lipid/water solubility, ionisation, disintegration and dissolution rate can influence the extent of absorption. Some excipients added to the drug were reported to be responsible of adverse effects for neonates and young children as they are not able to metabolise and eliminate them in the same manner as adults.
About malaria it is still very difficult to know if the resistance emergency is due to the poor quality of drugs, to the P. falciparum mutations or the inappropriate dosage regimens. For example some countries adopted the use of antimalarial combinations in their national policies, many favorable ideas have been reported after clinical studies proving the efficacy of SP+amodiaquine than given separately (Kenya, Uganda, Rwanda), but without looking for why resistance appeared with monotherapy.
About quinine, somebody knows why only tablets and injections are recognised in the essential drug list while those suspensions or syrups are not (and they are already on the market)? From which standard references those formulations are optimised to ensure therapeutic efficacy? How the bitter taste is masked in such formulations? How much sugar to add to the quinine suspension 100mg/5ml to hide bitter taste, when a score of 10 (the highest) was given to the 0.328mM quinine sulphate solution by the taste panel (Pharm. Res., vol 14 (6) pp720)! Probably a lot of sugar, while it was reported that liquid preparations containing propylene glycol or various sugars (sucrose, manitol, glucose) are responsible of diarrhoea and others symptoms or aggravate gastrointestinal distress that a patient is already experiencing. Those effects can be associated with the high
osmolarities noted when the mentioned excipients are used. Using such
suspensions, how to know whether that diarrhoea is from the sugar content or the febrile state of the patient? In case of resistance how to know the exact role of the drug?
Pierre Kayumba
Rwanda (studying in Belgium)
Pierre.Kayumba@UGent.be