European Journal of Clinical Pharmacology

, Volume 60, Issue 6, pp 397–402 | Cite as

Pharmacokinetics and pharmacodynamics of desmopressin administered orally versus intravenously at daytime versus night-time in healthy men aged 55–70 years

  • Asa Rembratt
  • Charlotte Graugaard-Jensen
  • Thomas Senderovitz
  • Jens Peter Norgaard
  • Jens Christian Djurhuus
Pharmacodynamics

Abstract

Objective

To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters.

Methods

The study had an open, randomised, four-way cross-over design. Desmopressin was administered orally (0.2 mg) and intravenously (2 µg), daytime and night-time, yielding four in-hospital sessions, separated by at least 2 days. Blood samples were taken before and at predetermined time points up to 12 h after dosing. Pharmacokinetic parameters were derived using a two-compartmental model except for AUC(0→t), which was derived using non-compartmental analysis. Bioavailability was estimated using AUC(0→t) for the oral and the intravenous periods. Urine, for measurements of volume and osmolality, was collected in predetermined intervals before and until 12 h after dosing.

Results

Fifteen healthy men aged 55–70 years were included in the analysis. The concentration–time curve after 2 µg intravenous desmopressin was best described using a biexponential term. The mean (95% CI) AUC at night was 302 (272–335) pg×h/ml and in the day was 281 (253–312) pg×h/ml. No statistically significant differences were detected between night and day except for terminal half-life, which was 3.1 h at night and 2.8 h in the daytime (P=0.02). After oral desmopressin, concentrations above the limit of quantification (2.5 pg/ml) were only detected in 51% of the samples. Peak plasma concentration (Cmax) was 6.2 (5.1–7.5) pg/ml at night and 6.6 (5.5–7.9) pg/ml in the daytime. Median time to reach Cmax (tmax) was 1.5 (range 1.0–4.1) h at night and 1.5 (range 0.5–3.0) h in the day. The bioavailability was 0.08%. The pharmacodynamic effects of oral and intravenous desmopressin given in the daytime were similar during the first 6 h after dosing. The night-time dosing and daytime intravenous dose resulted in antidiuresis throughout the measuring period, while the effect of the daytime peroral dose receded after 6 h.

Conclusion

The pharmacokinetic profile of desmopressin is biexponential. Terminal half-life was longer at night than in the daytime, but the difference is considered too small to be of clinical importance. The plasma levels given by the intravenous dose resulted in a duration of action of 12 h or more. Despite low bioavailability, the pharmacodynamic effects of oral desmopressin were similar in magnitude to those after intravenous dose at night and during the first 6 h after daytime administration.

Keywords

Pharmacokinetics Pharmacodynamics Desmopressin 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Asa Rembratt
    • 1
    • 3
  • Charlotte Graugaard-Jensen
    • 2
  • Thomas Senderovitz
    • 3
  • Jens Peter Norgaard
    • 3
  • Jens Christian Djurhuus
    • 2
  1. 1.Department of Clinical and Experimental PharmacologyLund University HospitalLundSweden
  2. 2.Department of Clinical Experimental ResearchSkejby University HospitalAarhusDenmark
  3. 3.Ferring Pharmaceuticals A/SCopenhagenDenmark

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