Gender difference in antidiuretic response to desmopressin

Juul, Kristian Vinter; Klein, Bjarke M.; Sandström, Rikard; Erichsen, Lars; Nørgaard, Jens Peter

doi:10.1152/ajprenal.00741.2010

Cited by 122 publications

(90 citation statements)

References 21 publications

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“…It was e.g. demonstrated in adults that there is a significant effect of sex on the DDAVP PD [38]. This effect is thought to be caused by a difference in V2-receptor expression [39] and should also be investigated in children.…”

Section: Discussionmentioning

confidence: 99%

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

et al. 2016

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Introduction: Desmopressin is used for nocturnal enuresis treatment in children. In this study, we investigated the pharmacokinetics of two formulations: a tablet and a lyophilisate, in both fasted and fed children.Methods: Previously published data from two studies (22 children aged 6 to 16 yr and 25 children aged 6 to 13 yr) were analyzed using population pharmacokinetic modeling. A 1-compartment model with first order absorption was fitted to the data. Covariates were selected using a forward selection procedure. The final model was evaluated, and sensitivity analysis was performed to improve future sampling designs. Simulations were subsequently performed to further explore the relative bioavailability of both formulations and the food effect.Results: The final model described the desmopressin plasma concentrations adequately.Formulation and fed state were included as covariates on the relative bioavailability. The lyophilisate was on average 32.1 % more available than the tablet, and fasted children exhibited an average increase in relative bioavailability of 101%, compared to fed children. Body weight was included as a covariate on distribution volume, using a power function with exponent 0.402.Simulations suggest both the formulation and the food effect are clinically relevant. Conclusions:Bioequivalence data of two formulations of the same drug in adults, cannot be readily extrapolated to children. This is the first study in children suggesting that the two desmopressin formulations in children are not bioequivalent at the currently approved dose levels.Furthermore, the effect of food intake was found to be clinically relevant. Sampling times for a future study were suggested. This sampling design should result in more informative data and consequently generate a more robust model. Key points Population pharmacokinetic modeling was applied to pediatric desmopressin PK data and used to extract more information out of existing pediatric drug data, generate new information and improve the collection of future information. In this study it was found that the established bioequivalence of desmopressin in adults might be different in the pediatric population. A profound food effect was also quantified. In order to make solid conclusions regarding desmopressin efficacy in children, PK and PD data should be gathered simultaneously in a well-designed study, for which some design suggestions are presented in this paper. Abbreviations

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Section: Discussionmentioning

confidence: 99%

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

et al. 2016

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“…Sex diff erences in occurrence of hyponatremia caused by AD were primarily associated with hormonal activity. Th us, estrogen (but not progesterone) stimulates the secretion of AVP [34], and women may have a higher sensitivity on ADH with an increase in the expression of vasopressin renal receptors [35]. However, there are studies, whose results have not shown the infl uence of sex on the incidence of hyponatremia with the use of AD therapy [2,21].…”

Section: Discussionmentioning

confidence: 99%

A case report of hyponatremia associated with maprotiline treatment

Stanković¹,

Pavlović²,

Jovičić³

et al. 2015

Hosp Pharm Int Multi J

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SUMMARYBackground: Maprotiline is a tricyclic antidepressant (sometimes classifi ed as a tetracyclic antidepressant), which is predominantly a norepinephrine/noradrenaline reuptake inhibitor, commonly prescribed for depression. Aim: To present a female patient with depressive episode and occurrence of hyponatremia during the maprotiline treatment. Case Report: A 62-year-old female was diagnosed with depressive episode four years ago. She was treated ambulatory with maprotiline 50mg/day and bromazepam 6mg/ day, from local psychiatrist. The patients also used enalapril 2x10 mg/day, metoprolol 2x50 mg/day, nifedipine 5 mg/day and simvastatin 20 mg/day for treating hypertension and dyslipidemia. After about 12 months of maprotiline use she was hospitalized at the Endocrinology unit of a local hospital due to appearance of confusion, unstable walking, cramps, as well as an increase in blood pressure. Then diagnosed hyponatremia (serum sodium level-112 mmol/L), corrected (137 mmol/L) by using parenteral therapy. The patient continued to use maprotiline without consultation with her psychiatrist. After one year, the patient was hospitalized at the Endocrinology unit of tertiary level due to detailed re-examination because of recurrent hyponatramia (117 mmol/L), corrected (136 mmol/L) by ambulatory use of parenteral therapy at a local hospital. Water test load was used and the Syndrome of inappropriate antidiuretic hormone secretion was diagnosed. Insulin Tolerance Test showed preserved the integrity of the hypothalamic-pituitary-adrenal axis. Antidepressant mirtazapine (15 mg/ day) was introduced due to recurrence of depression. Gradual reduction of depressive symptoms was observed to mirtazapine. Antihypertensive therapy, restriction of fl uid intake and dietary regimen were still applied. Serum sodium concentrations were in the normal ranges over the past 18 months. Conclusion: Serum sodium level should be measured before and during the therapy with any class of antidepressants, especially in those patients with increased risk of the hyponatremia occurrence.

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“…Beneficial effects both on short-term and long-term have been confirmed [19,20]. Adverse effects are limited; however, a risk for potentially fatal hyponatriemia has to be taken in account, definitely in an older population and in women who seem to be more prone to this adverse effect [21].…”

Section: Therapeutical Implicationsmentioning

confidence: 97%

Hormones and Nocturia: Guidelines for Medical Treatment?

Goessaert

Johan²,

Walle³

et al. 2013

J Steroids Horm Sci

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Nocturnal polyuria (NP) is an important cause of nocturia and it is related to an imbalance in water and/or sodium homeostasis. Antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) are believed to play an important role in this excessive urine production overnight, however, many other hormones are involved. ADH and ANP are both directly and indirectly influenced by the renin-angiotensin-aldosterone system (RAAS), prostaglandins antagonize both ADH and RAAS and sex hormones have a predominantly antidiuretic effect by stimulating ADH and RAAS, meaning that any disturbance can lead to an imbalance in diuresis. Since nocturia is a condition affecting sleep, melatonin secretion can also be affected, leading to a decrease in the antidiuretic effect and to an increase of nocturnal urine production. Depending on the underlying condition affecting any of these hormones, a more specific therapeutic approach might lead to a restoration of the normal diuresis cycle and to a good night's sleep. The characteristics of each of these hormones, the pathophysiology in NP and the therapeutic implications are set out in this review.

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Gender difference in antidiuretic response to desmopressin

Cited by 122 publications

References 21 publications

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

Effects of Food and Pharmaceutical Formulation on Desmopressin Pharmacokinetics in Children

A case report of hyponatremia associated with maprotiline treatment

Hormones and Nocturia: Guidelines for Medical Treatment?

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