Role of the Gastrointestinal Tract in the Regulation of Hydration in Man

Gebruers, E. M.; Hall, William J.

doi:10.1159/000171349

Cited by 3 publications

(2 citation statements)

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“…Intake of fluid increases excretion of water by the kidney. Inhibition of vasopressin secretion, decrease in the activity of renal sympathetic nerves or hormonal release are possible effector mechanisms in this response (Gebruers & Hall 1992). The suppression of vasopressin secretion is med-iated not only by osmo-and baroreceptors, also stimulation of oropharyngeal receptors is probably involved (Geelen et al 1996).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Antidiuretic Effect of Intravenous Administration of Desmopressin in Orally Overhydrated Male Volunteers

Callréus

Höglund

1998

Pharmacology & Toxicology

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Abstract:In order to study the antidiuretic activity of desmopressin in healthy human subjects, a study design has previously been used with subjects orally hydrated. The objective of the present study was to investigate the pharmacokinetics and the antidiuretic activity of desmopressin administered as an intravenous infusion to eight orally hydrated male volunteers. After initial ingestion of water corresponding to 15 ml . kg-l body weight, the overhydration was maintained by replacing the urinary fluid loss by drinking-water. Desmopressin (4 pg) was administered intravenously over 10 min. 1.5 hr after the start of the hydration procedure. Blood was sampled and urine was collected at intervals throughout the study day (9.5 hr). The terminal half-life of elimination (tl,z,) of desmopressin was calculated to be 2.9720.24 (S.E.M.) hr while the clearance was 1.7710.10 ml . min.-l a kg-I and the volume of distribution at steady state was 373t30 ml . kg-I. The infusion caused a marked and long-lasting reduction of the urine flow rate. Four hr after the start of the infusion the mean urine osmolality was 909246 mOsm. kg-l.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Antidiuretic Effect of Intravenous Administration of Desmopressin in Orally Overhydrated Male Volunteers

Callréus

Höglund

1998

Pharmacology & Toxicology

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“…Intake of fluid increases excretion of water by the kidney. Inhibition of vasopressin secretion, which decreases the activity of renal sympathetic nerves or hormonal release, is a possible effector mechanism in this response ( 29 ). The suppression of vasopressin secretion is mediated not only by osmo- and baroreceptors, but also, stimulation of oropharyngeal receptors is probably involved ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects

et al. 2019

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Purpose Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. Methods Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 μg and 0.12 μg desmopressin subcutaneous (SC) bolus injection. Results AV002 intranasal administration produced a time-to-maximum concentration (T max ) between 15 and 30 min and a maximum concentration (C max ) <10 pg/mL. C max and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 μg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5–6 h. Conclusions AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

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