Pharmacokinetics of Alprazolam in Geriatric Patients with Neurotic Depression

Dehlin, Ove; Kullingsjö, H.; Lidén, Anders; Agrell, Berit; Moser, Gabriele; Olsen, Ida Østrup

doi:10.1111/j.1600-0773.1991.tb02048.x

Cited by 6 publications

(8 citation statements)

References 12 publications

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“…Low concentrations of 4-hydroxyalprazolam were detected in serum while ca-hydroxyalprazolam was not detected at all following an oral dose of 0.5 mg alprazolam. This finding is consistent with the literature in that less than 10% of the dose is detected as metabolites in serum, with 4-hydroxyalprazolam as the major metabolite [29][30][31][32].…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.

Desai

et al. 1995

Brit J Clinical Pharma

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1 Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child-bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and a-hydroxy-alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2 Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4-Hydroxy-alprazolam was the predominant metabolite in serum samples while a-hydroxy-alprazolam was not detected.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.

Desai

et al. 1995

Brit J Clinical Pharma

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“…Six studies have evaluated the single and multiple-dose pharmacokinetics of alprazolam in the same individuals (Ciraulo et al 1986;Dehlin et al 1991;Fleishaker et al 1989;Kroboth et al 1990;Smith et al 1983;Wright & Chambers 1991). During the multiple-dosage phase of these studies, the duration of exposure was as long as 6 weeks (Dehlin et al 1991), and the daily dosage was as high as 9 mg/day (Ciraulo et al 1986).…”

Section: Intensive Design Studiesmentioning

confidence: 97%

“…Pharmacokinetic studies of nonradioactive alprazolam indicate that the a-and 4-hydroxy metabolites of alprazolam can be detected in plasma, but that concentrations of these metabolites (in unconjugated form) are considerably lower (less than 10%) than those of the intact drugs (Ciraulo et al 1990;Dehlin et al 1991;Kroboth et al 1990;Smith & Kroboth 1987).…”

Section: L Metabolic Pathway In Humansmentioning

confidence: 97%

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Clinical Pharmacokinetics of Alprazolam

Greenblatt

Wright

1993

Clinical Pharmacokinetics

341

108

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Alprazolam is a triazolobenzodiazepine that is extensively prescribed in the Western world for the treatment of anxiety and panic disorders. Its benzodiazepine receptor binding characteristics are qualitatively similar to those of other benzodiazepines. The drug is metabolised primarily by hepatic microsomal oxidation, yielding alpha-hydroxy- and 4-hydroxy-alprazolam as principal initial metabolites. Both have lower intrinsic benzodiazepine receptor affinity than alprazolam and appear in human plasma at less than 10% of the concentrations of the parent drug. Plasma concentrations of the 4-hydroxy metabolite exceed those of the alpha-hydroxy derivative, but urinary recovery of alpha-hydroxy-alprazolam greatly exceeds that of 4-hydroxy-alprazolam. This may be explained by chemical instability of 4-hydroxy-alprazolam in vitro. After single 1 mg oral doses in humans, typical pharmacokinetic variables for alprazolam are: a peak plasma concentration 12 to 22 micrograms/L occurring 0.7 to 1.8h postdose, a volume of distribution of 0.8 to 1.3 L/kg, elimination half-life of 9 to 16h and clearance of 0.7 to 1.5 ml/min/kg. Absolute bioavailability of oral alprazolam averages 80 to 100%. Pharmacokinetics are dose-independent and are unchanged during multiple-dose treatment. On average, mean steady-state plasma alprazolam concentrations change by 10 to 12 micrograms/L for each daily dosage change of 1 mg/day. Most studies show that alprazolam pharmacokinetics are not significantly influenced by gender. Clearance of alprazolam is reduced in many elderly individuals, even those who are apparently healthy. Clearance is significantly reduced in patients with cirrhosis. Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and some data suggest reduced free clearance of alprazolam in such patients. Pharmacokinetics of alprazolam are not significantly altered in abstinent alcoholics or patients with panic disorder, and are not influenced by the phase of the menstrual cycle in women. Coadministration of cimetidine, fluoxetine, fluvoxamine or propoxyphene significantly impairs alprazolam clearance. However, alprazolam clearance is not altered by coadministration of propranolol, metronidazole, disulfiram, oral contraceptives or ethanol. Imipramine clearance may be impaired if alprazolam is coadministered. Alprazolam does not alter the pharmacokinetics of digoxin. Although a therapeutic concentration range is not clearly established, some studies indicate that optimal reduction of anxiety associated with panic disorder occurs at steady-state plasma alprazolam concentrations of 20 to 40 micrograms/L. Concentrations higher than this may be needed for suppression of the actual panic attacks. Side effects associated with alprazolam (drowsiness, sedation, etc.) are consistent with its primary benzodiazepine agonist action and increase in frequency with higher steady-state plasma concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…7 Two other studies of ALP clearance in the elderly did not use a comparison group of young controls. 8,9 Age-dependent reductions in clearance of drugs metabolized by microsomal oxidation have been demonstrated in many other studies. 10±16 Inducibility of metabolism in the elderly has received little attention.…”

Section: Introductionmentioning

confidence: 96%