The relationship between buspirone bioavailability and dose in healthy subjects

Buspirone is an anxiolytic drug given at a dosage of 15 mg/day. The mechanism of action of the drug is not well characterised, but it may exert its effect by acting on the dopaminergic system in the central nervous system or by binding to serotonin (5-hydroxytryptamine) receptors. Following a oral dose of buspirone 20 mg, the drug is rapidly absorbed. The mean peak plasma concentration (Cmax) is approximately 2.5 micrograms/L, and the time to reach the peak is under 1 hour. The absolute bioavailability of buspirone is approximately 4%. Buspirone is extensively metabolised. One of the major metabolites of buspirone is 1-pyrimidinylpiperazine (1-PP), which may contribute to the pharmacological activity of buspirone. Buspirone has a volume of distribution of 5.3 L/kg, a systemic clearance of about 1.7 L/h/kg, an elimination half-life of about 2.5 hours and the pharmacokinetics are linear over the dose range 10 to 40 mg. After multiple-dose administration of buspirone 10 mg/day for 9 days, there was no accumulation of either parent compound or metabolite (1-PP). Administration with food increased the Cmax and area under the plasma concentration-time curve (AUC) of buspirone 2-fold. After a single 20 mg dose, the Cmax and AUC increased 2-fold in patients with renal impairment as compared with healthy volunteers. The Cmax and AUC were 15-fold higher for the same dose in patients with hepatic impairment compared with healthy individuals. The half-life of buspirone in patients with hepatic impairment was twice that in healthy individuals. The pharmacokinetics of buspirone were not affected by age or gender. Coadministration of buspirone with verapamil, diltiazem, erythromycin and itraconazole substantially increased the plasma concentration of buspirone, whereas cimetidine and alprazolam had negligible effects. Rifampicin (rifampin) decreased the plasma concentrations of buspirone almost 10-fold.

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“…The pharmacokinetics of buspirone were found to be linear over the dose range 10 to 40mg when given orally to 24 healthy volunteers. [21]…”

Section: Dose Proportionalitymentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug

Mahmood

Sahajwalla

1999

Clinical Pharmacokinetics

284

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“…The starting dose for buspirone is 5 mg TID or 7.5 mg BID. Because of its linear pharmacokinetics and short half-life, it is possible to increase the dosage by 5 mg/day every 2–3 days until a target of 20–30 mg/day, divided into two or three daily doses, is reached 73. If, after several weeks, adequate clinical improvement has not been obtained, it is possible to titrate up to a maximum dosage of 60 mg/day.…”

Section: Treatmentmentioning

confidence: 99%

Management of the psychological comorbidities of dermatological conditions: practitioners' guidelines

Connor¹

2017

CCID

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Dermatological disease can be devastating for patients, and although dermatologists are focused on remedying the cutaneous manifestations of these conditions, it is easy to miss the psychological suffering lurking below. Studies reveal that psychiatric comorbidity in dermatology is highly prevalent. Undetected psychopathology can greatly decrease a patient’s quality of life and even contribute significantly to the clinical severity of their skin disease. For these reasons, it is vital that practitioners learn to detect psychological distress when it is present, and it is equally essential that they understand the treatment options available for effective intervention. Without training in psychiatric diagnosis and psychopharmacology, dermatologists can easily feel overwhelmed or out of their comfort zone when faced with the need to manage such conditions, but with the negative stigma associated with psychiatric disease in general, a psychiatric referral is often refused by patients, and the dermatologist is thus left with the responsibility. Uncertainty abounds in such situations, but this review seeks to alleviate the discomfort with psychodermatological disease and share practical and impactful recommendations to assist in diagnosis and treatment. In a busy dermatology clinic, the key is effective and efficient screening, combined with a repertoire of pharmacological and non-pharmacological treatment options that can be dispersed through an algorithmic approach according to the specific findings of that screening. By implementing these recommendations into practice, dermatologists may begin to gain comfort with the management of psychocutaneous disease and, as a specialty, may expand to fill a hole in patient care that is truly significant for patients, their families, and our communities as a whole.

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“…The relationship between dose and bioavailability was evaluated in 24 healthy males age 22-40 years using 10,20, and 40 mg.55, 56 The elimination half-life. T , , , and AUC were not dose related.…”

Section: Pharmacokinetics and Metabolismmentioning

confidence: 99%

Buspirone: An Update on a Unique Anxiolytic Agent

Jann

1988

Pharmacotherapy

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Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.

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The relationship between buspirone bioavailability and dose in healthy subjects

Cited by 27 publications

References 2 publications

Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug

Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug

Management of the psychological comorbidities of dermatological conditions: practitioners' guidelines

Buspirone: An Update on a Unique Anxiolytic Agent

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The relationship between buspirone bioavailability and dose in healthy subjects

Cited by 27 publications

References 2 publications

Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug

Clinical Pharmacokinetics and Pharmacodynamics of Buspirone, an Anxiolytic Drug

Management of the psychological comorbidities of dermatological conditions: practitioners&#39; guidelines

Buspirone: An Update on a Unique Anxiolytic Agent

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Management of the psychological comorbidities of dermatological conditions: practitioners' guidelines