Some Aspects of Pharmacokinetics of Proguanil in Nigeria Subjects.

Olowu, Adekunle Olatunde (1986)

Thesis

The effect of age on the elimination kinetics of proguanil, a prophylactic antimalarial drug, was investigated in forty volunteers drawn equally from four different age groups. The cumulative amount of proguanil excreted unchanged in urine was monitored in the forty -volunteers following oral administration of a single dose of 100 mg Proguanil Hydrochloride Tablet (Paludrine) after an overnight fast. Aliquots of the urine samples collected at predetermined intervals of time up to 48 hours were analysed by the modified spectrophotometric method of Gage and Rose (1946). The mean cumulative amounts excreted in urine for 48 hours (D48) were subjected to statistical analysis by applying both the analysis of variance and the new Duncan's Multiple Range Tests. The statistical analysis revealed that the mean D48 in the adults (30-40 years) was significantly higher (p< 0.01) than the value obtained for the two lower age groups (8-18 years and 19-29 years) while it was not significantly different (p > 0.05) from the value for the middle age group (41-51 years).The mean Du value for the 19 - 29 years group was also significantly higher (p 0.05) than that of the youngest age group (8 - 18 years). There occurred a correlation (r = 0.95) between the average weight of the different age groups and the mean cumulative amounts of unchanged drug excreted in urine by the groups. On the whole, the results showed that with increase in age up to 40 years, there seems to occur a gradual and significant increase (p<0.05) in the percentage of an oral dose of proguanil excreted unchanged in human urine in 48 hours. The maximum excretion rate and time of maximum excretion rate data respectively exhibited a similar increase in value with increase in age up to 40 years. It is suggested that this increase may be an indication of the differences in the metabolic or the overall elimination kinetics of the drug in the different age groups.

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