Originals

European Journal of Clinical Pharmacology

, Volume 22, Issue 1, pp 21-25

Impaired effect of sulfonylurea following increased dosage

  • E. Wåhlin-BollAffiliated withDepartment of Community Care SciencesDepartment of Clinical Pharmacology, Malmö General HospitalDepartment of Internal Medicine (Lund University Hospital), University of Lund
  • , G. SartorAffiliated withDepartment of Community Care SciencesDepartment of Clinical Pharmacology, Malmö General HospitalDepartment of Internal Medicine (Lund University Hospital), University of Lund
  • , A. MelanderAffiliated withDepartment of Community Care SciencesDepartment of Clinical Pharmacology, Malmö General HospitalDepartment of Internal Medicine (Lund University Hospital), University of Lund
  • , B. SchersténAffiliated withDepartment of Community Care SciencesDepartment of Clinical Pharmacology, Malmö General HospitalDepartment of Internal Medicine (Lund University Hospital), University of Lund

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Summary

Ten Type 2 diabetics were examined during long-term treatment, at two dosage levels, with chlorpropamide once daily and glipizide t.i.d. Drug concentrations were measured by gas chromatography and high-pressure liquid chromatography, respectively, plasma insulin (IRI) by radio-immunoassay, and blood glucose enzymatically. Both drugs gave continuous sulfonylurea exposure, even at the lower dosage, and the mean plasma concentrations were almost doubled after the increase in dose. Neither the IRI nor the glucose response to meals showed any therapeutic improvement following the increase in chlorpropamide dosage. The lower dosage of glipizide produced better glucose utilization than chlorpropamide. On the other hand, the increased dose of glipizide led to impairment instead of further improvement. As this was associated with enhanced rather than reduced IRI levels, the impairment might have been due to increased peripheral insulin resistance. Thus, glipizide offers a therapeutic advantage over chlorpropamide, but its effectiveness may be restricted not only by limitations set by the disease, but also by counter-regulatory mechanisms that develop during continuous exposure to sulfonylureas at high levels.

Key words

diabetics chlorpropamide glipizide dosage increase impaired effect blood glucose plasma insulin