Geriatric patient pharmacokinetics

Aniracetam (6), launched in 1993 in both Japan and Italy for the treatment of cognition disorders, is in Phase II trials in the United States as of this writing. In clinical studies it has been shown to cause some improvement in elderly patients with mild to moderate mental deterioration (63), and in geriatric patients with cerebral insufficiency (64). In a multicenter double-blind placebo-controUed trial involving 109 patients with probable AD, positive effects were observed in 36% of patients after six months of treatment (65), a result repeated in a separate study of 115 patients (66). A review of the biological and pharmacokinetic properties, and clinical results of aniracetam treatment in cognitively impaired individuals is available (49). 

The stereoselective pharmacokinetics of the selective serotonin reuptake inhibitor, citalopram, have been studied in 10 healthy young subjects [139]. After administration of 40 mg racemate daily for 21 days by the oral route, stereoselectivity was found in citalopram plasma concentrations. The R(—) S(+) ratios of Cmax and AUCss were 1.5 and 1.6, respectively. No difference was noted in suggesting similar absorption rates of the enantiomers. The terminal phase values were 47 and 35 h for the R and S enantiomers, respectively. Renal clearance comprised 20% of each enantiomer s total clearance and was nonstereoselective. Although both enantiomers are extensively metabolized, both possess low hepatic extraction ratios [139]. Serotonin reuptake inhibition of citalopram primarily resides with the S enantiomer (see Chap. 5, Sec. 3.4 for more details), which attains lower concentrations in plasma. In eight geriatric patients (mean 77 y) given... 

Special population pharmacokinetics (for geriatric subjects, renal, and hepatic impairment), obtained after a single dose of 80 mg fexofenadine hydrochloride, were compared to those for normal subjects from a separate study of similar design. While subject weights were relatively uniform between studies, these adult special population patients were substantially older than the healthy, young volunteers. Thus, an age effect may be confounding the pharmacokinetic differences observed in some of the special populations. 

Perform pharmacokinetic studies in special population (geriatric or pediatric age groups, renal or hepatic impaired patients, various ethnic groups, and drug-drug interaction studies) groups, if appropriate. 

The pharmacokinetics of fluoxetine in healthy geriatric individuals do not differ substantially from those in younger adults. Because of its relatively long half-life and nonlinear pharmacokinetics, the possibility of altered pharmacokinetics in geriatric individuals could exist, particularly those with systemic disease and/or in those receiving multiple medications concurrently. The elimination half-lives of fluoxetine and norfluoxetine do not appear to be altered substantially in patients with renal or hepatic impairment. 

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