Diazoxide disposition and effect on vascular resistance and compliance in dogs.

Ogilvie, Richard I.

doi:10.1161/01.hyp.3.2.225

Hypertension

1981

DOI: 10.1161/01.hyp.3.2.225

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Diazoxide disposition and effect on vascular resistance and compliance in dogs.

Richard I. Ogilvie¹

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1982

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Cited by 3 publications

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“…8 -""" Stable isotope dilution mass fragmentography extended the t 1 /2 from 20 to 53 hours in four subjects* 8 with extensive biotransformation, as less than one-third of a dose appeared unchanged in the urine. The HPLC assay used in the present study is specific and sensitive without interference from the major metabolite, 14 and the prolonged time of observation allowed definition of a long plasma 11/2 of 47.6 hours, with a range of 32.0 to 62.5 hours (table 2). The variation in apparent volumes of distribution between subjects was somewhat less than the variation in half-lives.…”

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confidence: 91%

Diazoxide concentration-response relation in hypertension.

Ogilvie¹,

Nadeau²,

Sitar³

1982

Hypertension

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1 -* After a 300 mg i.v. bolus dose, blood pressure is maximally reduced in 2 minutes, then rises rapidly over the next 10 to 40 minutes to a plateau level that is maintained for a variable length of time.*-* This same dose of diazoxide administered over a longer period has been observed to have a plateau effect of less magnitude and shorter duration.4 ' ' It was postulated that, because diazoxide is highly protein-bound, the high plasma-free diazoxide

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confidence: 91%

Diazoxide concentration-response relation in hypertension.

Ogilvie¹,

Nadeau²,

Sitar³

1982

Hypertension

Self Cite

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Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia

et al. 2017

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Background: Diazoxide is the first-line treatment for pediatric hyperinsulinemic hypoglycemia (HI). This study aimed to elucidate the pharmacokinetics of diazoxide in children with HI. Methods: We obtained 81 blood samples from 22 children with HI. Measured serum diazoxide concentrations were used for population pharmacokinetic analysis. Patient factors influencing pharmacokinetics were estimated using nonlinear mixed-effects model analysis. Relationships between drug exposure and adverse drug reactions were also investigated. Results: Diazoxide disposition in the body was described by a 1-compartment model. Oral clearance (CL/F) and the volume of distribution were proportional to body weight (WT), as expressed by CL/F in males (liters/h) = 0.0358 + 0.00374 × WT (kg). CL/F in females was 39% greater than that in males. Steady-state concentrations of diazoxide were similar following twice- and 3 times-daily dosing when the total daily doses were comparable. A patient whose serum diazoxide concentration exceeded 100 μg/mL over a 4-month period developed hyperglycemia. No significant correlation was observed between severity of hirsutism and diazoxide concentration. Conclusion: We have proposed for the first time a population pharmacokinetic model for diazoxide in children with HI. The potential risk of diabetes mellitus and/or hyperglycemia increases when serum concentrations of diazoxide exceed 100 μg/mL.

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Diuretic treatment in essential hypertension

1983

Current Medical Research and Opinion

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In North America, diuretics remain the most common first-line drug therapy for essential hypertension based on efficacy, safety and cost. The promotion of step-care programmes has firmly established their dominant use on this continent whereas in Europe, particularly in Scandinavia and Great Britain, beta-adrenoceptor blocking agents are more frequently chosen as first-line therapy. On both continents, combined therapy with a diuretic and a beta-blocker is probably the most common second step for patients with blood pressures uncontrolled on a single agent alone and diuretics remain useful, if not essential, to prevent sodium retention commonly observed with other antihypertensive agents. Although the forced loss of sodium and water may be responsible for their initial antihypertensive effect, the mechanism underlying their long-term effect is unknown but probably involves some alteration of vascular smooth muscle reactivity. More recently, concern has been expressed about their long-term safety as larger populations are being exposed to diuretic agents for a significant proportion of their life-span. These concerns include haemodynamic and biochemical consequences of diuretic therapy - excessive tachycardia at rest and with minimal exercise, postural hypotension, hypokalaemia and arrhythmias, muscle cramps or fatigue, glucose intolerance, hyperuricaemia and altered circulating lipids as markers or promotors of atherosclerosis and its complications. At present, there is insufficient evidence to alter the present recommendation of diuretic agents as first-line drug therapy in the treatment of hypertension.

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Diazoxide disposition and effect on vascular resistance and compliance in dogs.

Cited by 3 publications

References 20 publications

Diazoxide concentration-response relation in hypertension.

Diazoxide concentration-response relation in hypertension.

Population Pharmacokinetics of Diazoxide in Children with Hyperinsulinemic Hypoglycemia

Diuretic treatment in essential hypertension

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