BACKGROUND: Pharmacokinetic parameters of sedative-hypnotic medications can be influenced by age and gender. OBJECTIVE: This study analyzed pharmacokinetic parameters of zolpidem, formulated as a sublingual zolpidem tartrate tablet (ZST; Intermezzo®), in healthy elderly males and females (mean age 72 years) and in non-elderly males and females (34 years). METHODS: This was a randomized, single-dose, open-label, two-way crossover study evaluating pharmacokinetic parameters of 1.75 and 3.5 mg dosages of ZST in elderly subjects (n = 22), and 3.5 mg dosages ofZSTin non-elderly subjects (n = 24). Main outcome measures were pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC), maximum observed concentration (C(max)), time to reach C(max) (T(max)), elimination half-life (T(½)), and apparent oral clearance (CL/F). RESULTS: Dose proportionality in zolpidem exposure was maintained between 1.75 and 3.5 mg doses for both elderly females and males. With administration of the 3.5 mg dose of ZST to elderly and non-elderly subjects, significantly higher systemic exposure was seen in elderly females (C(max) +44.6 %, P < 0.01; AUC +40.4 %) compared with non-elderly females. However, systemic exposure was only modestly higher in elderly males compared with non-elderly males. Greater exposure was seen in elderly females compared to males (C(max) +46.8 %, P < 0.01; AUC +31.4 %). In this study, exposure between non-elderly females and males was equivalent. Changes in T(½) and T(max) values were not observed, with no significant age effect on oral clearance. There were no apparent differences in tolerability among age and gender groups. CONCLUSION:Elderly individuals were found to have higher C(max) and AUC values compared with non-elderly subjects. C(max) and AUC were greater in elderly women compared with elderly men.
RCT Entities:
BACKGROUND: Pharmacokinetic parameters of sedative-hypnotic medications can be influenced by age and gender. OBJECTIVE: This study analyzed pharmacokinetic parameters of zolpidem, formulated as a sublingual zolpidem tartrate tablet (ZST; Intermezzo®), in healthy elderly males and females (mean age 72 years) and in non-elderly males and females (34 years). METHODS: This was a randomized, single-dose, open-label, two-way crossover study evaluating pharmacokinetic parameters of 1.75 and 3.5 mg dosages of ZST in elderly subjects (n = 22), and 3.5 mg dosages of ZST in non-elderly subjects (n = 24). Main outcome measures were pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC), maximum observed concentration (C(max)), time to reach C(max) (T(max)), elimination half-life (T(½)), and apparent oral clearance (CL/F). RESULTS: Dose proportionality in zolpidem exposure was maintained between 1.75 and 3.5 mg doses for both elderly females and males. With administration of the 3.5 mg dose of ZST to elderly and non-elderly subjects, significantly higher systemic exposure was seen in elderly females (C(max) +44.6 %, P < 0.01; AUC +40.4 %) compared with non-elderly females. However, systemic exposure was only modestly higher in elderly males compared with non-elderly males. Greater exposure was seen in elderly females compared to males (C(max) +46.8 %, P < 0.01; AUC +31.4 %). In this study, exposure between non-elderly females and males was equivalent. Changes in T(½) and T(max) values were not observed, with no significant age effect on oral clearance. There were no apparent differences in tolerability among age and gender groups. CONCLUSION: Elderly individuals were found to have higher C(max) and AUC values compared with non-elderly subjects. C(max) and AUC were greater in elderly women compared with elderly men.
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