A pharmacokinetic and pharmacodynamic study of desmopressin: evaluating sex differences and the effect of pre-treatment with piroxicam, and further validation of an indirect response model
| Autor: | E. Bodil Roth, Johanna Mercke Odeberg, Peter Höglund, Torbjörn Callréus, Stefan Lundin |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.drug_class Pharmaceutical Science Pharmacology Piroxicam Hemostatics Sex Factors Pharmacokinetics Internal medicine medicine Humans Nocturia Deamino Arginine Vasopressin Drug Interactions Desmopressin business.industry Anti-Inflammatory Agents Non-Steroidal Middle Aged Models Theoretical medicine.disease Endocrinology Area Under Curve Pharmacodynamics Injections Intravenous Diabetes insipidus Urine osmolality Female Vasopressin Analogue medicine.symptom business Diabetes Insipidus hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 56:1389-1398 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1211/0022357044535 |
| Popis: | Desmopressin is a synthetic vasopressin analogue mainly used in treatment of diabetes insipidus and nocturia. Studies in rats have revealed a sex difference in the response to a vasopressin infusion, which was diminished after treatment with an NSAID. This study was performed in man to investigate the influence of sex and concomitant treatment of piroxicam on the pharmacokinetics and dynamics of desmopressin, and to validate a previously described indirect response model. Eight healthy males and eight healthy females participated in the trial, which was conducted in a pharmacokinetic (PK) part followed by a pharmacodynamic (PD) part. Desmopressin was administered intravenously as a single dose (PK = dose 2 μg, PD = dose 0.2 μg). Piroxicam was administered to achieve steady state. The pharmacokinetic parameters of desmopressin were estimated and calculated by means of two-compartmental analysis. In the dynamic part a study design based on an oral hydration model was used. Parameters for urine flow and urine osmolality were estimated. Individual estimates of the pharmacokinetic parameters served as input to the indirect response model that subsequently was fitted to urine osmolality data. The pharmacokinetics of desmopressin after a fixed bolus injection was neither influenced by piroxicam nor sex of the subject. The pharmacodynamics of desmopressin showed a sex difference where females exhibited a more pronounced antidiuretic effect than males, which was statistically significant when the effects were submaximal (>4.5 h after dose). The sex differences were diminished after pre-treatment with piroxicam, indicating a prostaglandin PGE2-mediated mechanism. The indirect response model was confirmed, although the modelling could not distinguish a sex difference, indicating a limitation of this model compared with traditional descriptive statistics. |
| Databáze: | OpenAIRE |
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