ABSTRACT
OBJECTIVE: To evaluate digoxin pharmacokinetic parameters using Bayesian estimation in 60 patients, and to identify factors that appeared to affect the risk of digoxin toxicity. PATIENTS AND METHODS: 60 patients with serum digoxin concentrations were evaluated retrospectively. We collected demographic, clinical and laboratory data, and information on concurrent medications and clinical and electrocardiographic features of digoxin toxicity. The incidence of digoxin toxicity was evaluated in 50 patients. Serum digoxin concentrations were measured with fluorescence polarisation immunoassay Individual pharmacokinetic parameters were estimated by Bayesian method using Abbottbase Pharmacokinetic Systems. RESULTS: Signs of digoxin toxicity were present in 23 patients (46%). Patients without signs of digoxin toxicity had a significantly lower mean serum digoxin concentration than patients with signs, 1.99 ± 0.9 µg/L vs 2.7 ± 1.5 µ.g/L, respectively (p = 0.047). Patients with serum digoxin concentrations >2.2 µg/L differed significantly from those with values ≤2.2 µg/L, respectively, for the following parameters: age (82.0 ± 8.0 vs 72.0 ± 16.0 years; p = 0.005), serum creatinine levels (133.0 ± 55.0 vs 106.0 ± 26.0 µmo1/L; p = 0.012), bodyweight (57.4 ± 12.8 vs 69.2 ± 17.8kg; p = 0.01), volume of distribution (208.5 ± 89.5 vs 315.7 ± 91.2L; p = 0.0001), total clearance (1.60 ± 0.65 vs 3.4 ± 1.5 L/h; p = 0.0001), and elimination half-life (94.2 ± 28.6 vs 72.4 ± 16.7h; p = 0.001). Estimation of optimal dose showed that the doses recommended in intoxicated patients should be 3.5 times lower to reach the therapeutic range. CONCLUSION: Digoxin concentrations were higher in patients with toxicity. Older age enhanced the risk of digoxin toxicity. Monitoring digoxin concentrations may help to confirm suspected digitalis toxicity.
ABSTRACT
Cyclophosphamide given in association with corticosteroids has markedly improved the prognosis of systemic vasculitis. Little information has been reported on cyclophosphamide pharmacokinetics in these diseases and data evaluating its metabolite, 4-hydroxycyclophosphamide/aldophosphamide, pharmacokinetics and concentrations are lacking. Cyclophosphamide was administered as a 1-h intravenous infusion every 3 weeks for six cycles to ten vasculitis patients. Serum cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations were assayed on the first cycle of the treatment by reversed-phase high-pressure liquid chromatography with ultraviolet detection. The mean (+/- SD) 4-hydroxycyclophosphamide/aldophosphamide and cyclophosphamide areas under the serum concentration-time curves were, respectively, 1.86 +/- 1.12 and 154.1 +/- 62.7 mg/L x h with a ratio of 1.30 +/- 0.76%. The mean maximum serum 4-hydroxycyclophosphamide/aldophosphamide was reached 2.3 h after cyclophosphamide administration. The mean (+/- SD) cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide half-lives were, respectively, 5.5 +/- 3.1 and 7.6 +/- 2.3 h. The results are consistent with those obtained for cancer patients, in spite of a wide interpatient variability of concentrations and pharmacokinetic parameters.
Subject(s)
Cyclophosphamide/metabolism , Cyclophosphamide/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Phosphoramide Mustards/metabolism , Vasculitis/metabolism , Adult , Aged , Aged, 80 and over , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Vasculitis/drug therapyABSTRACT
Specific features of nosocomial infections in patients aged 70 years or older admitted to a short-term care medical department in a 400-bed general hospital were studied to assist in designing nosocomial infection control programs for this population. Data from five annual prevalence surveys were evaluated retrospectively. The 517 patients aged 70 years or older were compared to the 1093 patients younger than 70 years. The older patients were more likely to have risk factors for nosocomial infections including severe disease (36.2% vs 19.1%; P < 10(-6)), referral from another department (24.6% vs 17.5%; P < 0.01), a long hospital stay duration (8.5 days vs 3.5 days), mechanical ventilation (4.3% vs 1.6%; P < 0.01), an indwelling urinary catheter (12.0% vs 4.0%; P < 10(-7)), and a long median duration of urinary catheterization (6 days vs 2 days). The prevalence of nosocomial infections was increased nearly two-fold in the older patients (10.3% vs 5.6%; P < 0.01), although the difference was statistically significant only for urinary tract infections (5.4% vs 1.4%; P < 10(-5)), particularly in patients without urinary catheters. After exclusion of all patients with urinary tract infections, the prevalence of nosocomial infections was similar in the older and younger patients (4.3% vs 3.7%) despite a persistently higher frequency of risk factors for nosocomial infection in the older group. These results indicate that urinary tract infection should be the main target of programs aimed at minimizing nosocomial infection in elderly patients admitted to short-term care facilities. Faultless technique is essential during urinary catheter insertion. High-quality nursing care contributes substantially to the prevention of urinary tract infection in noncatheterized patients with urinary incontinence or neurologic disorders.
