Disposition kinetics of buspirone in patients with renal or hepatic impairment after administration of single and multiple doses

Abstract

The single dose and steady-state pharmacokinetics of buspirone and its metabolite 1-pyrimidinyl piperazine (1-PP) have been evaluated in normal volunteers and patients with renal or hepatic impairment, using a parallel group design, with assignment of patients to study group on the basis of the degree of renal (mild, moderate, severe) or hepatic (compensated or decompensated) impairment. Each healthy volunteer or patient received a single dose of 10 mg buspirone on Day 1 of the study, and starting 36 h after the first dose, healthy volunteers and patients received 10 mg doses of buspirone every 12 hours for 9 days. On the morning of Day 10 they received the last dose. Serial blood samples were collected on Days 1, 5 and 10 and plasma was analysed for buspirone and 1-PP. The plasma concentrations of buspirone and 1-PP were highly variable regardless of the renal or hepatic function. The peak concentrations (Cmax) and area under the curves (AUC) of buspirone and 1-PP on Days D5 and 10 were higher than on Day D1. The trough levels (Cmin) and AUCs (D5 and 10) of buspirone and 1-PP indicated, that, regardless of renal or hepatic function, steady state was reached after 3 to 5 days of dosing. At steady-state, patients with renal or hepatic impairment had significantly higher Cmax and AUC values of buspirone than in normal volunteers. However, the intensity and frequency of adverse experiences in patients with renal or hepatic impairment were not significantly different from those observed in normal volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Steady-state pharmacokinetics of nefazodone in subjects with normal and impaired renal function

“…Consistent with these findings are the results of single [7] and multiple-dose [21] studies which demonstrated that subjects with hepatic impairment exhibit increased systemic exposure and longer tl/2 values for NEF, HO-NEF and mCPR Subjects in the three treatment groups in the present study had normal liver function which, in the absence of an effect of renal impairment, explains why the pharmacokinetics of nefazodone and its two metabolites were comparable among groups. The lack of significant effect of renal impairment on systemic exposure or elimination of nefazodone and its metabolites is consistent with observations for other drugs which are eliminated mainly by hepatic metabolism, such as buspirone [22] and the selective serotonin reuptake inhibitor drugs, fluoxetine [23] and sertraline [24]. Further findings in this study are more related to drug metabolic capacity than renal function.…”

Tolerability, Pharmacokinetics, and Neuroendocrine Effects of PRX‐00023, a Novel 5‐HT1A Agonist, in Healthy Subjects

“…Unlike the azapirones (eg, buspirone, gepirone, tandospirone), PRX‐00023 has high affinity for only the 5‐HT1A receptor. The high affinity of PRX‐00023 for the 5‐HT1A receptor (K i ≅ 5–11 nM), combined with minimal binding to other receptors such as alpha‐1 (K i ≅ 1600 nM), alpha‐2 (K i ≅ 3000 nM), and dopamine D2 (K i > 2000 nM), may explain the minimal vasoactive effects and other adverse effects relative to buspirone 9 , 10 . In addition, PRX‐00023 cannot be converted to the alpha‐2 antagonist 1‐(2‐pyrimidimyl)‐piperazine, which has been linked to cardiovascular effects 11 .…”

“…The high affinity of PRX-00023 for the 5-HT1A receptor (K i ≈ 5-11 nM), combined with minimal binding to other receptors such as alpha-1 (K i ≈ 1600 nM), alpha-2 (K i ≈ 3000 nM), and dopamine D2 (K i > 2000 nM), may explain the minimal vasoactive effects and other adverse effects relative to buspirone. 9,10 In addition, PRX-00023 cannot be converted to the alpha-2 antagonist 1-(2-pyrimidimyl)-piperazine, which has been linked to cardiovascular effects. 11 Based on these better selectivity profiles, these investigations were conducted to evaluate the tolerability of a range of single and multiple doses of PRX-00023 with a few titration steps in healthy subjects.…”

“…12 The half-life range of PRX-00023 at doses ranging from 10 Figure 3. Mean prolactin change from baseline versus time profile following multiple oral dose administration of PRX-00023 (10,30,40, and 60 mg qd) or placebo in healthy subjects on day 28 (protocol PRX-00023-CP-002).…”

Psychotherapeutic Agents in End‐Stage Renal Disease

“…Buspirone is an anxiolytic which is pharmacologically distinct from benzodiazepines. The pharmacokinetics of buspirone have been studied in patients with CKD and in those with ESRD undergoing HD (90,91). Renal impairment has been associated with increased buspirone concentration, however statistically significant differences have not been demonstrated.…”