Medicine (Austin & Northern Health) - Theses

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The pharmacokinetics and pharmacodynamics of calcium antagonists

Razak, Tariq Bin Abdul ( 1988)

This thesis describes the development of a specific, sensitive and reliable method for the simultaneous measurement of the parent drug and one of its metabolites at nanogram/ml levels for the dihydropyridines - nicardipine and. PY-108-068 in plasma. It demonstrates the application of pharmacokinetic principles and their relationship to the pharmacodynamic properties of these compounds. Increased systemic bioavailability of nicardipine with a corresponding increase in pharmacodynamic effect is shown in patients with liver disease, demonstrating the importance of the hepatic first-pass metabolism for this compound. Saturation kinetics are demonstrated for the PY-108-068 within the single dose range of 50-200mg orally. Age and concominant food ingestion does not significantly affect the elimination half-lives of PY- 108-068. This study demonstrates that PY-108-068 is more effective in lowering the blood pressure of patients in the old age-group, as compared to that in the young age-group, and that inhibition of reflex tachycardia occurs at higher blood levels than those producing a vasdilator effect. There is good correlations between plasma levels and blood pressure response for both nicardipine and PY-108-068.