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A pharmacokinetic a...
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.
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- Mercke Odeberg, Johanna (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine
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Callréus, Torbjörn (författare)
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- Lundin, Stefan, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för de kirurgiska disciplinerna, Avdelningen för anestesiologi och intensivvård,Institute of Surgical Sciences, Department of Anaesthesiology and Intensive Care
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- Roth, Bodil (författare)
- Lund University,Lunds universitet,Gastroenterologi,Forskargrupper vid Lunds universitet,Klinisk koagulationsmedicin, Malmö,Gastroenterology,Lund University Research Groups,Clinical Coagulation, Malmö
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- Höglund, Peter (författare)
- Lund University,Lunds universitet,Avdelningen för klinisk kemi och farmakologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Chemistry and Pharmacology,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2010-02-18
- 2004
- Engelska.
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Ingår i: The Journal of pharmacy and pharmacology. - : Oxford University Press (OUP). - 0022-3573 .- 2042-7158. ; 56:11, s. 1389-98
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 microg, PD = dose 0.2 microg). 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 PGE(2)-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Nyckelord
- Adult
- Anti-Inflammatory Agents
- Non-Steroidal
- pharmacology
- Area Under Curve
- Deamino Arginine Vasopressin
- administration & dosage
- pharmacokinetics
- pharmacology
- Diabetes Insipidus
- drug therapy
- Drug Interactions
- Female
- Hemostatics
- administration & dosage
- pharmacokinetics
- pharmacology
- Humans
- Injections
- Intravenous
- Male
- Middle Aged
- Models
- Theoretical
- Piroxicam
- pharmacology
- Sex Factors
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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