Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024523 (malabsorption)
 7,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve patients with chronic mucocutaneous candidosis were treated orally with ketoconazole (doses, 200-400 mg daily) for a mean period of six months. Seven of the patients had one of the following abnormalities: congenital endocrinopathy syndrome, an autosomal recessive or autosomal dominant defect in which candidosis is not associated with endocrinopathy, or the malabsorption syndrome. All patients had fungal infections of the mouth, and 11 had onychomycosis. Two patients were also infected with dermatophytes. At the end of treatment, 10 patients were cured of oral infection, and 11 with nail infections showed significant improvement. Marked improvement of hand and foot infections was also recorded. Patients infected with dermatophyte fungi had the poorest responses to therapy. The mean (+/- SD) MIC for isolates of Candida albicans from eight patients was 0.95 (+/- 0.78) microgram/ml. Clinical and biochemical monitoring showed no toxicity, and no resistant fungi emerged during treatment. Results of this initial study of ketoconazole for treatment of severe and recalcitrant superficial infections indicate the need for further assessment of this drug, which appears to offer a simple, nontoxic, and effective treatment of fungal infections.
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PMID:Treatment of chronic mucocutaneous candidosis with ketoconazole: a study of 12 cases. 625 39

Ciprofloxacin is a fluoroquinolone antibiotic effective in the treatment of lower respiratory tract infections (LRTI). The aim of this study was to assess the pharmacokinetic appropriateness of a standard switch i.v./os regimen of ciprofloxacin (200 mg i.v. bid for 3 to 5 days followed by 500 mg os bid for 7 to 10 days) frequently used in routine clinical practice in the treatment of elderly patients with mild to moderate LRTI. The pharmacokinetic study was performed on a cohort of 17 elderly inpatients. Blood samples were collected in steady state conditions at appropriate intervals. Ciprofloxacin serum concentrations were analyzed using an HPLC method and pharmacokinetic parameters were estimated using the WinNonlin software package. The pharmacokinetic data were at least partially different from those obtained by other authors in elderly patients (lower Cmax after i.v. administration and higher CL both after i.v. and oral administration). Cmax after a 1-hour 200-mg infusion were similar to those observed during the 500 mg bid peroral regimen (2.1 +/- 0.9 mg/L vs 2.6 +/- 1.0 mg/L; p = 0.054). The absolute oral bioavailability (84.1%) allowed a total body exposure 2.1-fold greater after 500 mg bid oral administration than after 200 mg bid i.v. administration (AUC(0-tau) 11.4 +/- 4.3 mg/L x h vs 5.5 +/- 1.8 mg/L x h). The results show that in malabsorption-free elderly patients a regimen of 500 mg os bid may be considered a valid therapeutic approach from the beginning of therapy for mild to moderate LRTI caused by sensitive microorganisms (MIC < 0.1 mg/L). In fact, because the peak serum level to MIC ratio (Cmax/MIC) and the area under the inhibitory serum concentration-time curve (AUIC24 = AUC24h/MIC) are actually considered major pharmacodynamic determinants for the outcome of treatment with fluoroquinolones, this regimen could guarantee both a better pharmacokinetic exposure than the 200 mg i.v. bid regimen and a cost-effective treatment of LRTI. However, because of the great pharmacokinetic interindividual variability observed a normalized dosage per kg (3 mg/kg/12h i.v. and 8 mg/kg/12h os) should be considered, especially for body weight >90 kg and, whenever possible, TDM of AUC(0-tau) or at least of Cmax should be performed to individualize therapy in this subpopulation.
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PMID:Ciprofloxacin disposition in elderly patients with LRTI being treated with sequential therapy (200 mg intravenously twice daily followed by 500 mg per os twice daily): comparative pharmacokinetics and the role of therapeutic drug monitoring. 1094 76

Tuberculosis (TB) is a leading cause of infectious death. Nontuberculous mycobacteria (NTM) cause a wide variety of difficult-to-treat infections in various human hosts. Therapeutic drug monitoring (TDM) remains a standard clinical technique that uses plasma drug concentrations to determine dose. The reason to do this is simple: drug exposure (that is, the free drug area under the plasma concentration-time curve) relative to the MIC and not the dose per se largely determines the outcome of the infections. TDM provides objective information that clinician can use to make informed dosing decisions. The normal plasma concentration ranges provide reasonable guidance for initial target concentrations. Clinicians then combine concentration data with knowledge about the patients, in order to decide how aggressive to be with dosing. With sicker patients, who are closer to a poor outcome, one may be willing to accept an increased risk of potential toxicity in order to secure patient survival. In the clinic, time and resources are limited, so typically only two samples are collected postdose. The 2-h postdose concentrations approach the peak for most TB and NTM drugs. A 6-h sample allows the clinician to distinguish between delayed absorption and malabsorption, because patients with the latter need higher doses in order to gain the benefit associated with standard doses. Plasma concentrations do not account for all of the variability in patient responses to TB or NTM treatment, and concentrations cannot guarantee patient outcomes. However, combined with clinical and bacteriological data, TDM can be a decisive tool, allowing clinicians to look inside of their patients and adjust doses based on objective data. Knowing the dose, rather than guessing at the dose, is the path to shorter and more successful treatment regimens.
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PMID:The Role of Therapeutic Drug Monitoring in Mycobacterial Infections. 2808 9