Gender differences in v2 agonists with focus on polyuric conditions
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Gender Differences in V2 Agonists With focus on polyuric conditions. Dr. Kristian Vinter Juul, D.V.M PhD-student University of Ghent Medical Science Director Medical Science Urology Ferring International PharmaScience Centre Copenhagen. Female rats express significantly more V2R mRNA.

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Gender differences in v2 agonists with focus on polyuric conditions

Gender Differences in V2 AgonistsWith focus on polyuric conditions

Dr. Kristian Vinter Juul, D.V.M

PhD-student University of Ghent

Medical Science Director Medical Science Urology Ferring International PharmaScienceCentre Copenhagen


Female rats express significantly more v2r mrna
Female rats express significantly more V2R mRNA

  • Liu et al 2010: Female rats express significantly more V2R mRNA and protein in kidneys than males

  • Hypothesis: this results physiologically in a greater sensitivity to V2R agonist administration[1]

Liu J, et al: Sex Differences in Vasopressin V2 Receptor Expression and Vasopressin-InducedAntidiuresis. Am J Physiol Renal Physiol December 1, 2010


Gender difference "masked" by high exposure?

Figure 1, Dose/Response curve for dDAVP/AVP)


X-Escape and AVPR2

The V2-receptor is located on the X-chromosome:

It is possible that the gene for V2 can escape inacti-vation. This will give higher density of receptors in women and a greater response to Desmopressin


Data used in this exploratory analysis

Weiss JP, Zinner NR, Klein BM, Nørgaard JP. Neurourol Urodyn. 2012 Apr;31(4):441-7. doi: 10.1002/nau.22243. Epub 2012 Mar 22.


Mean desmopressin concentration profiles by dose and gender, successive tests of covariates log(age), gender, and log(weight)

Table 1: Successive tests (top-down) of covariate effects on Desmopressin AUC and Cmax


Gender difference in CS29 successive tests of covariates log(age), gender, and log(weight)


Nocturnal Urine Volume successive tests of covariates log(age), gender, and log(weight)

  • Tests of covariate effects showed that the gender difference in weight‑corrected ED50 was statistically significant (p=0.009)

  • The relative sensitivity (ED50 for males/ ED50 for females) is estimated at 2.7 with a 95% CI of 1.3-8.1

Parameter estimates for the nocturnal urine volume model


Long-term durability of gender successive tests of covariates log(age), gender, and log(weight)difference confirmed

Mean decrease in # nocturnal voids

Mean decrease in number of nocturnal voids (25–50 µg ODT) was greater for females than males

Juul et al, NAU, 2012


Treatment effect relative to placebo effect cs40 females
Treatment effect relative to Placebo effect. CS40. Females successive tests of covariates log(age), gender, and log(weight)

Sand et al, J Urol, 2013


Treatment effect relative to placebo effect cs41 males
Treatment effect relative to Placebo effect. CS41. Males successive tests of covariates log(age), gender, and log(weight)

Weiss et al, J Urol, 2013


Conclusion successive tests of covariates log(age), gender, and log(weight)

  • In conclusion, differences in pharmacodynamic response leads to a dose recommendation in adult nocturia patients, stratified by gender:

For females 25 µg seemed to be an optimal, efficacious and safe dose while similar efficacy is expected for males at a dose level approximately 2-3 times higher


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