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Abstract

Relationship between the pharmacokinetic and pharmacodynamic profile of nilvadipine in the dog.

W H Wu, B M Henderson, R Lanc, D Garnes, A Yacobi and B M Silber
Drug Metabolism and Disposition March 1988, 16 (2) 222-227;
W H Wu
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B M Henderson
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R Lanc
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D Garnes
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A Yacobi
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B M Silber
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Abstract

The purpose of this study was to determine the pharmacokinetic profile of nilvadipine and, using a chronic dog model, determine whether there was a correlation between plasma concentrations of the drug and hemodynamic effects. Nilvadipine was given to four dogs as single intravenous (iv) and oral doses. Pharmacokinetic parameters were estimated after each dose using model-independent methods. The mean elimination half-life was approximately 6 hr after both iv and oral doses. The absolute bioavailability of nilvadipine decreased from 67 to 27% after increasing oral doses (6 and 24 mg), probably because of reduced drug absorption from the gastrointestinal tract. Nilvadipine produced plasma concentration-related decreases in diastolic (DBP) and systolic (SBP) blood pressure and reflex increases in heart rate. The maximum reduction in DBP and SBP ranged from 34 to 53% and 17 to 47%, respectively, from control and was attained at about 0.1 and 0.7 hr after iv and oral doses, respectively. A strong linear correlation between the per cent reduction in both DBP (r = 0.9; p less than 0.001) and SBP (r = 0.66; p less than 0.001) and log plasma concentration of nilvadipine was established. The slopes of the concentration-response relationships were virtually superimposable after both iv and oral routes of administration. A plasma concentration of about 10 and 16 ng/ml was associated with a 14% reduction in DBP or SBP, respectively. There was no clear relationship between plasma concentrations of nilvadipine and changes in heart rate.

 

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Drug Metabolism and Disposition
Vol. 16, Issue 2
1 Mar 1988
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Abstract

Relationship between the pharmacokinetic and pharmacodynamic profile of nilvadipine in the dog.

W H Wu, B M Henderson, R Lanc, D Garnes, A Yacobi and B M Silber
Drug Metabolism and Disposition March 1, 1988, 16 (2) 222-227;

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Abstract

Relationship between the pharmacokinetic and pharmacodynamic profile of nilvadipine in the dog.

W H Wu, B M Henderson, R Lanc, D Garnes, A Yacobi and B M Silber
Drug Metabolism and Disposition March 1, 1988, 16 (2) 222-227;
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