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Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.

Purpose: Desmopressin is a standard treatment for monosymptomatic nocturnal enuresis. Different formulations are promoted as bioequivalent, although these claims are not supported by comparative pharmacodynamic data in children. Food interaction is known to influence the bioavailability of desmopressin. We compared the pharmacodynamics of the 2 most frequently used desmopressin formulations, tablet and lyophilizate, with a standardized meal, allowing extrapolation to clinical reality, where the interval between evening meal and medication intake is limited for school-age children. We hypothesized there would be a faster pharmacodynamic response, and greater concentrating and antidiuretic activity for the fast dissolving (melt) formulation compared to the tablet with simultaneous food intake., Materials and Methods: Two tests were performed on separate days in identical standardized conditions, starting with a 15 ml/kg water load. After achieving maximal diluting capacity a standardized meal was administered, followed by desmopressin tablet (t test) or melt (M-test). Diuresis rate and urinary osmolality were measured hourly. Paired data from 4 girls and 15 boys with a mean age of 12.1 years were obtained., Results: In the early response phase more than 25% of patients had a higher diuresis rate with tablet vs melt formulation, reaching statistical significance in the plateau phase (urine collected at hours 3 to 5, p <0.02) and in duration of action (urine collected at hours 5 to 8, p <0.005). For desmopressin melt smaller standard deviations in diuresis rate were remarkable. Concentrating capacity demonstrated no significant differences between formulations in the early response phase, in contrast to the plateau phase (p <0.036) and duration of action (p <0.001)., Conclusions: With meal combination desmopressin melt formulation has a superior pharmacodynamic profile to tablet, making it more suitable for the younger age group with a limited interval between meal and drug administration., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Primary nocturnal enuresis is a heterogeneous disorder, causing a mismatch between overnight diuresis volume and functional bladder capacity. Despite increasing insights in pathogenesis, lack of efficacy of the available treatments is a major problem. We evaluated characteristics of bladder volume and diuresis rate in patients with nocturnal enuresis referred to a tertiary enuresis center., Materials and Methods: Noninvasive screening including maximal voided volume, 24-hour circadian rhythm of diuresis and osmotic excretion from 1,000 consecutive patients., Results: Of the patients referred as having monosymptomatic nocturnal enuresis 32% were subsequently classified as having nonmonosymptomatic nocturnal enuresis. Differences in bladder volume and nocturnal diuresis characteristics between the monosymptomatic nocturnal enuresis and nonmonosymptomatic nocturnal enuresis groups were minimal., Conclusions: The most common observation is a nocturnal diuresis volume greater than maximal voided volume, which in both groups can be caused by nocturnal polyuria or small bladder volume for patient age. The most striking observation is that the positive correlation between nocturnal diuresis volume rate and nocturnal osmotic excretion and 24-hour fluid intake is significantly higher than with the inversed urinary osmolality overnight, which is not only unexpected based on the theory of the primary suppression of vasopressin levels overnight, but also points to a more important role for nutritional and fluid intake than accepted, if not in the primary pathogenesis, then at least in therapy resistance.

Purpose: The anti-incontinence effect of desmopressin resides in its concentrating capacity and antidiuretic properties. We compared nighttime urine production on wet and dry nights in a highly selected study population of children with monosymptomatic nocturnal enuresis associated with proved nocturnal polyuria who responded only partially to intranasal desmopressin., Materials and Methods: We retrospectively analyzed 39 home recordings of nocturnal urine production and maximum voided volume in children 7 to 19 years old (median 8.9) with monosymptomatic nocturnal enuresis with nocturnal polyuria who had a partial response to desmopressin. Nocturnal diuresis volume and maximum voided volume were documented at baseline (14 days) and during 3 months of followup., Results: Baseline nocturnal urine output (439 +/- 39 ml) was significantly higher than the maximum voided volume (346 +/- 93 ml, p <0.01). During desmopressin treatment nocturnal urine output on wet nights (405 +/- 113 ml) differed significantly from that on dry nights (241 +/- 45 ml). During treatment nocturnal urine output on wet nights did not differ from baseline values., Conclusions: Persistence of nocturnal polyuria on wet nights in partial desmopressin responders may be related to an insufficient antidiuretic effect. In addition to poor compliance and suboptimal dosing, the poor bioavailability of intranasal desmopressin may be a pathogenic factor. Further prospective studies are needed.

Purpose: We evaluated pretreatment values of circadian rhythm of urine production and urine osmolality in children with different subtypes of monosymptomatic nocturnal enuresis, and investigated their predictive value for desmopressin response., Materials and Methods: We assessed 125 consecutive patients with monosymptomatic nocturnal enuresis, nocturnal polyuria and normal functional bladder capacity who were treated with desmopressin for a median of 17 months (range 3 to 100). Patients were characterized according to the desmopressin response as full responders or nonfull responders. Baseline parameters were obtained from a 2-week home recording diary. Results were compared with 125 consecutive children with monosymptomatic nocturnal enuresis and reduced functional bladder capacity., Results: No differences in pretreatment values of functional bladder capacity, circadian rhythm of urine production or urine osmolality were found between desmopressin full responders and nonfull responders. Patients with nocturnal polyuria had a significantly higher 24-hour diuresis volume compared to children with reduced functional bladder capacity. Some children with reduced functional bladder capacity also had nocturnal polyuria., Conclusions: Our findings show that the characteristics of nocturnal polyuria in patients with monosymptomatic nocturnal enuresis and normal functional bladder capacity do not predict desmopressin response. The wide overlap among the different subgroups suggests that dividing patients with monosymptomatic nocturnal enuresis into those with reduced functional bladder capacity and those with desmopressin responsive nocturnal polyuria might be insufficient. Patients with nocturnal polyuria and normal functional bladder capacity have a significantly higher daytime and nighttime diuresis volume compared to children with reduced functional bladder capacity, suggesting a direct correlation between daytime fluid intake and nocturnal diuresis rate. Some children with reduced functional bladder capacity also have nocturnal polyuria.

Purpose: There is increasing evidence that a subgroup of patients with monosymptomatic nocturnal enuresis and nocturnal polyuria resistant to desmopressin may have an abnormal circadian rhythm of renal tubular sodium handling. The pathogenesis of this phenomenon remains to be elucidated. If the increased sodium excretion overnight results in desmopressin resistance, decreasing the sodium excretion overnight may result in subsequently better desmopressin response. Materials and Methods: We conducted a pilot study of the anti-enuretic and antidiuretic effects of desmopressin combined with 0.5 mg/kg furosemide daily in patients with desmopressin resistant nocturnal polyuria despite dietary sodium and protein restriction. Values were plotted against the reference frame of a desmopressin responsive enuresis group. Results: Baseline values revealed significantly lower urinary osmolality and higher diuresis rate overnight compared to the reference population (monosymptomatic nocturnal enuresis desmopressin responders). Introduction of desmopressin resulted in normalization of nocturnal urinary osmolality. However, nocturnal polyuria persisted, despite reaching maximal urinary concentration overnight. Although protein and sodium restriction resulted in a significant decrease in urinary osmolality and diuresis rate, the difference was not clinically important enough to reach normal values or to achieve continence. Furosemide in the morning resulted in a significant increase in diuresis and osmotic and sodium excretion during the day, and decreased nighttime diuresis and osmotic excretion. In 9 of 12 patients the nocturnal antidiuretic effect resulted in an anti-enuretic effect, defined as enuresis less than 1 wet night per month. In 3 patients insufficient anti-enuretic effects were obtained despite significant antidiuresis. Conclusions: This pilot study clearly demonstrates that introduction of early morning furosemide results in a significantly lower nocturnal diuresis rate. Reduced diuresis associated with unchanged urinary osmolality results in decreased nocturnal osmotic excretion in compensation for increased osmotic (sodium) excretion during the daytime. [Copyright &y& Elsevier]