A. A. Silver, H. Wishinsky, R. F. Caplan
Sep 1, 1959
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Influential Citations
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Quality indicators
Journal
Annals of the New York Academy of Sciences
Abstract
Reviewing the Boehringer Reports1 on Wp-40 (metahexamide) prior to our study, we observed that when the authors used single doses of 500 mg. and 1 gm. of metahexamide, they found half-value periods of 20 and 22.5 hours, respectively. We chose to use daily doses of 150 mg. of metahexamide, the recommended safe therapeutic dose,* in our studies. Half-value studies or the disappearance rate of metahexamide from the serum were studied, using the 150-mg. dose in order to relate these values to the previously mentioned 500 mg. and 1 gm. doses. Thirteen diabetic and 12 nondiabetic patients that had not previously received metahexamide were given, while fasting, a single oral dose of 150 mg. of the drug. Blood specimens were drawn prior to drug therapy and then 1, 2,3, 5 7,9, 12, and 24 hours after ingesting the metahexamide. Serum levels of metahexamide were determined using the method of Bratton and Marshall! FIGURE 1shows the number of hours after ingestion of the drug for appearance of peak serum levels of metahexamide. FIGURE 2 shows the number of hours required for the peak level of metahexamide in the serum to drop to the half-peak level. Although the range in the nondiabetic group is considerably less than that in the diabetic group, both groups showed wide variations. Our results appear to M e r substantially from those reported by the Boehringer group. FIGURE 3 represents the percentage of metahexamide remaining in the serum 19 hours after peak level of the drug. The choice of 19 hours after peak level was one of expediency. Percentages were calculated by dividing the serum concentration of metahexamide 19 hours after peak level by its concentration at peak level. It is apparent that the nondiabetics as a group demonstrate lower concentrations of serum metahexamide 19 hours after peak level than the diabetic group. The diabetic subjects seem to fall into 2 groups, 1 group showing 19-hour postpeak levels very similar to those of the controls, the other showing high levels of serum metahexamide. The parenthetical letters G and P indicate those patients who later, on continuous therapy, showed (G) good clinical control and (P) poor clinical control. It is obvious that no conclusion can be drawn from the single dose test in determining the value of this compound in the treatment of any given patient, with our limited number of pa-