Disease relevance of CTRC

• OBJECTIVE: To evaluate the ability of CT with rectal contrast medium (CTRC) to diagnose a normal appendix in children with abdominal pain [1].
• The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR [2].
• 1. Roxatidine acetate, a new histamine H2-receptor antagonist, was administered in the evening (75 mg p.o.) to eight patients with renal insufficiency (CLCR 8-17 ml min-1) for 12 days and plasma drug concentrations were measured [3].
• One hundred and thirty-one patients with chronic renal insufficiency (Clcr between 20-50 ml/min) because of primary renoparenchymal diseases and proteinuria < or =1.0 g/day, were randomized to Lisinopril (L=66) or alternative antihypertensive therapy (C=65) [4].
• Dibekacin pharmacokinetics was studied in 3 healthy volunteers, 5 patients with renal failure presenting Clcr, between 4.0 and 67 ml min-1 per 1.73 m2 of body surface and 5 anephric patients given as a 30 minute intravenous infusion [5].

High impact information on CTRC

• Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen [6].
• Consistent with this notion, the pancreatitis-associated mutation A16V in cationic trypsinogen increases the rate of chymotrypsin C-mediated processing of the activation peptide 4-fold and causes accelerated trypsinogen activation in vitro [6].
• CONCLUSIONS: The pharmacokinetics of omapatrilat, the only clinically relevant active compound studied, was independent of CLCR [7].
• For omapatrilat and S-methylphenylmercaptopropionic acid, neither Cmax nor AUC(0-T) was CLCR dependent [7].
• Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.001) [8].

Chemical compound and disease context of CTRC

• Because Clcr correlated directly with nizatidine renal clearance, Clcr values may be used to estimate nizatidine dosage reductions in renal insufficiency [9].
• The half-life of elimination was 2.59 h in normal subjects and was unchanged in mild renal failure (creatinine clearance, CLCR 90-60 ml/min/1.48 m2) but was increased to 4.72 h in moderate renal failure (CLCR 60-30 ml/min/1.48 m2), and to 12.07 h in severe renal failure (CLCR below 30 ml/min/1.48 m2) [10].
• Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2 [11].
• Nineteen hypertensive patients, nine of them with chronic renal failure (CLCR 38.9 vs 102.3 ml.min-1 1.73 m-2), were investigated after peroral administration of a combination of antipyrine (500 mg, in capsules) and nifedipine (10 mg, in Oxcord capsules) in the morning after an overnight fast [12].

Biological context of CTRC

• Plasma concentrations (Cmax and AUC) of ciprofloxacin and its M1 and M2 metabolites were significantly increased in subjects with reduced Clcr values (Clcr < 60 mL/min/1.73 m2) compared with normal subjects (Clcr > 90 mL/min/1.73 m2) [13].
• The aim of the present investigation was to test the efficacy of WBR in estimating bone mineralization rate (m) and to evaluate the influence of renal function (Clcr) and bone mass (forearm bone mineral content; BMC) on WBR [14].
• Both the kaliuresis and the calciuresis during tau were tightly correlated with the natriuresis over the broad range of CLCR [15].
• In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Clcr, which was accompanied by an increase in Cldig from 57.5 +/- 32, and 60.7 +/- 27.3 (duplicate measurements) to 103.9 +/- 55.4 (p less than 0.01) and 103.8 +/- 46.5 ml min-1 (p less than 0.01) [16].
• Group 1 patients had an average CLR:CLCR ratio greater than 1 for both the parent compound and the metabolite, suggesting that net tubular secretion was still intact, despite a diminished glomerular filtration rate (CLCR = 24 ml.min-1.73 m-2).(ABSTRACT TRUNCATED AT 250 WORDS)[17]

Associations of CTRC with chemical compounds

• There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance [2].
• Peak ceforanide levels (mean = 69 +/- 12 micrograms/ml) and volumes of distribution did not vary with creatinine clearance (Clcr, ml/min/1.73 m2) and both plasma clearance and renal clearance decreased linearly as Clcr decreased [18].
• Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours [19].
• A positive correlation was observed between ciprofloxacin clearance (Cl) and Clcr with a slope of 0.29 (r2 = 0.78) and between renal clearance (Clr) and Clcr with a slope of 0.19 (r2 = 0.84) [13].
• Renal clearance of pentamidine (Clr) decreased over time but always exceeded the Clcr, indicating tubular secretion [20].
• In the high Ca(2+) environment of the duodenum, chymotrypsin C facilitates trypsinogen activation, whereas in the lower intestines, chymotrypsin C promotes trypsin degradation as a function of decreasing luminal Ca(2+) concentrations [21].

Analytical, diagnostic and therapeutic context of CTRC

• BACKGROUND: The aim of this retrospective study is to assess the accuracy of single slice helical CT scan with intravenous, and rectal contrast (CTRC) in the diagnosis of acute appendicitis (AA) in patients with suspected AA, with particular analysis of the diagnostic signs [22].
• METHODS: Oral omapatrilat, 10 mg/d, was administered for 8 to 9 days to three groups of eight subjects with varying degrees of renal function (CLCR values, normal > or = 80; mild to moderate impairment < 80 to > or = 30; severe impairment < 30 mL/min/1.73 mL2) and to six subjects undergoing maintenance hemodialysis [7].
• The drug was administered by intravenous short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min) [23].

References