The racemic selective serotonin reuptake inhibitor citalopram (CIT) is increasingly used for depressive disorders. As both enantiomers of CIT differ in pharmacologic activity and demethylated metabolites might contribute to the antidepressent action of CIT, a stereoselective assay for all active compounds is needed, but will require that pharmacokinetic/pharmacodynamic relationships be investigated. A stereoselective high-performance liquid chromatography (HPLC)-assay (Chirobiotic V column) with UV-detection (lambda = 240 nm) for R- and S-CIT as well as both enantiomers of desmethyl(DM)-CIT and didesmethyl(DDM)-CIT was developed. The calibration range was linear from 5 to 200 ng/mL and the lower limit of detection averaged 2 ng/mL. Based on three quality controls (10, 75, and 150 ng/mL) the intraday and interday coefficients of variation ranged from 1.3% to 9.0% for CIT and from 2.2% to 10.3% for DM-CIT and DDM-CIT. The assay was used to analyze the trough steady state plasma levels of all 6 agents in 16 elderly patients treated daily with 20 to 40 mg CIT. For the dose of 20 mg (n = 14) mean values +/- SD of R- (and S-CIT) averaged 36.2+/-15.0 (27.4+/-13.1) ng/mL, respectively (mean R/S-ratio: 1.4+/-0.4), for R- (and S-DM-CIT) 7.2+/-3.1 (7.7+/-3.8) ng/mL, respectively (R/S-ratio: 1.0+/-0.3) whereas DDM-CIT was only detectable as R-enantiomer in 8 cases (13.2+/-12.1 ng/mL; range: 2.2-36.2 ng/mL). Significant (p < 0.01) linear correlations could be found between both enantiomers of CIT and DM-CIT as well as between parent drug and primary metabolite for the R-enantiomers. Apparently R/S- and metabolic ratios increased with dose; this might indicate that stereoselective disposition of CIT and DM-CIT is concentration-dependent. The present assay allows a rapid, sensitive, and reliable stereoselective determination of CIT and its (active) metabolites which can be applied for assessing pharmacokinetic parameters and evaluating putative relationships to clinical (side) effects.

OBJECTIVES:To examine the effects of various risk factors on three functional outcomes during rehabilitation. SETTING: Geriatric inpatient rehabilitation unit. DESIGN: Observational longitudinal study. PARTICIPANTS: One hundred sixty-one geriatric rehabilitation inpatients (men, women), mean age 82, who were capable of walking at baseline. MEASUREMENTS: Functional status was assessed weekly between admission and discharge and at a followup 4 months later at home using the function component of the Short FormFLate Life Function and Disability Instrument, the Barthel Index, and Habitual Gait Speed. Various risk factors, such as falls-related self-efficacy (Falls Efficacy Scale-International), were measured. Associations between predictors and functional status at discharge and follow-up were analyzed using linear regression models and bivariate plots. RESULTS: Fear of falling predicted functioning across all outcomes except for habitual gait speed at discharge and follow-up. Visual comparison of functional trajectories between subgroups confirmed these findings, with different levels of fear of falling across time in linear plots. Thus, superior ability of this measure to discriminate between functional status at baseline across all outcomes and to discriminate between functional change especially with regard to the performance-based outcome was demonstrated. CONCLUSION: Falls-related self-efficacy is the only parameter that significantly predicts rehabilitation outcome at discharge and follow-up across all outcomes. Therefore, it should be routinely assessed in future studies in (geriatric) rehabilitation and considered to be an important treatment goal. J Am Geriatr Soc 58:664-673, 2010.

The SF-LLFDI is a reliable and valid self-report instrument to measure functional status in geriatric rehabilitation inpatients. It improves the assessment of clinically relevant responsiveness. Further research is warranted to improve its sensitivity to change.