The Effect of Acetylsalicylic Acid, Caffeine, and Codeine on the Excretion of Phenacetin Metabolites

1972 ◽  
Vol 50 (8) ◽  
pp. 809-816 ◽  
Author(s):  
M. Henry Gault ◽  
Nasrollah T. Shahidi ◽  
Alec Gabe
Keyword(s):  
Renal Failure ◽  
Urinary Excretion ◽  
Creatinine Clearance ◽  
Acetylsalicylic Acid ◽  
Total N ◽  
Drug Ingestion

The urinary excretion of total N-acetyl-p-aminophenol and conjugates (NAPA) and total 2-hydroxyphenetidin and conjugates (2-OHP) was studied after ingestion of 2 g phenacetin alone and also in combination with acetylsalicylic acid, caffeine, and codeine (APC and C). NAPA excretion was measured in 17 patients; seven had taken the combination analgesic preparation in large amounts for 5 or more years and 11 had values for creatinine clearance of < 50 ml/min. NAPA excretion was measured for 96 h after drug ingestion and 2-OHP for at least 24 h in 15 patients of the same group. Excretion of total NAPA and 2-OHP was significantly reduced when phenacetin was ingested as APC and C compared with excretion when phenacetin was given alone. In the presence of renal failure NAPA excretion was merely delayed, whereas 2-OHP excretion was reduced or absent.

scholarly journals Predictors of Postoperative Acute Renal Failure after Noncardiac Surgery in Patients with Previously Normal Renal Function

2007 ◽  
Vol 107 (6) ◽  
pp. 892-902 ◽  
Author(s):  
Sachin Kheterpal ◽  
Kevin K. Tremper ◽  
Michael J. Englesbe ◽  
Michael O’Reilly ◽  
Amy M. Shanks ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Creatinine Clearance ◽  
Normal Renal Function ◽  
Noncardiac Surgery ◽  
Intraoperative Management ◽  
All Cause Mortality ◽  
Calculated Creatinine Clearance ◽  
Preoperative Predictors

Background The authors investigated the incidence and risk factors for postoperative acute renal failure after major noncardiac surgery among patients with previously normal renal function. Methods Adult patients undergoing major noncardiac surgery with a preoperative calculated creatinine clearance of 80 ml/min or greater were included in a prospective, observational study at a single tertiary care university hospital. Patients were followed for the development of acute renal failure (defined as a calculated creatinine clearance of 50 ml/min or less) within the first 7 postoperative days. Patient preoperative characteristics and intraoperative anesthetic management were evaluated for associations with acute renal failure. Thirty-day, 60-day, and 1-yr all-cause mortality was also evaluated. Results A total of 65,043 cases between 2003 and 2006 were reviewed. Of these, 15,102 patients met the inclusion criteria; 121 patients developed acute renal failure (0.8%), and 14 required renal replacement therapy (0.1%). Seven independent preoperative predictors were identified (P &lt; 0.05): age, emergent surgery, liver disease, body mass index, high-risk surgery, peripheral vascular occlusive disease, and chronic obstructive pulmonary disease necessitating chronic bronchodilator therapy. Several intraoperative management variables were independent predictors of acute renal failure: total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration. Acute renal failure was associated with increased 30-day, 60-day, and 1-yr all-cause mortality. Conclusions Several preoperative predictors previously reported to be associated with acute renal failure after cardiac surgery were also found to be associated with acute renal failure after noncardiac surgery. The use of vasopressor and diuretics is also associated with acute renal failure.

Chronic renal failure in a mouse model of human adenine phosphoribosyltransferase deficiency

1998 ◽  
Vol 275 (1) ◽  
pp. F154-F163 ◽  
Author(s):  
Michael G. Stockelman ◽  
John N. Lorenz ◽  
Frost N. Smith ◽  
Gregory P. Boivin ◽  
Amrik Sahota ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Kidney Disease ◽  
Creatinine Clearance ◽  
Renal Damage ◽  
Male Mice ◽  
Adenine Phosphoribosyltransferase ◽  
Disease Treatment ◽  
Significant Impairment ◽  
Normal Males

In humans, adenine phosphoribosyltransferase (APRT, EC 2.4.2.7 ) deficiency can manifest as nephrolithiasis, interstitial nephritis, and chronic renal failure. APRT catalyzes synthesis of AMP from adenine and 5-phosphoribosyl-1-pyrophosphate. In the absence of APRT, 2,8-dihydroxyadenine (DHA) is produced from adenine by xanthine dehydrogenase (XDH) and can precipitate in the renal interstitium, resulting in kidney disease. Treatment with allopurinol controls formation of DHA stones by inhibiting XDH activity. Kidney disease in APRT-deficient mice resembles that seen in humans. By age 12 wk, APRT-deficient male mice are, on average, mildly anemic and smaller than normal males. They have extensive renal interstitial damage (assessed by image analysis) and elevated blood urea nitrogen (BUN), and their creatinine clearance rates, which measure excretion of infused creatinine as an estimate of glomerular filtration rate (GFR), are about half that of wild-type males. APRT-deficient males treated with allopurinol in the drinking water had normal BUN and less extensive visible renal damage, but creatinine clearance remained low. Throughout their lifespans, homozygous null female mice manifested significantly less renal damage than homozygous null males of the same age. APRT-deficient females showed no significant impairment of GFR at age 12 wk. Consequences of APRT deficiency in male mice are more pronounced than in females, possibly due to differences in rates of adenine or DHA synthesis or to sex-determined responses of the kidneys.

Dosage Regimen Adjustments in Renal Impairment

1973 ◽  
Vol 7 (9) ◽  
pp. 382-387 ◽  
Author(s):  
Donald L. Giusti ◽  
William L. Hayton
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Dosage Regimen ◽  
Drug Dosage ◽  
Loading Dose ◽  
Dosage Regimens ◽  
Drug Dosage Regimen ◽  
Pharmacokinetic Approach

A pharmacokinetic approach based on creatinine clearance has been outlined which permits drug dosage regimen adjustments in patients with renal impairment. The parameters needed for calculating a loading dose and a maintenance regimen are the fraction of a dose excreted unchanged in the urine, the creatinine clearance of the patient, and the half-life of the drug in patients with normal renal function. In varying degrees of renal failure, predicted dosage regimens agree closely with dosage regimens predicted by other methods for a number of drugs.

Diflunisal, a New-Acting Analgesic and Prostaglandin Inhibitor: Effect of Concomitant Acetylsalicylic Acid Therapy on Ototoxicity and on Disposition of Both Drugs

1979 ◽  
Vol 7 (1) ◽  
pp. 61-68 ◽  
Author(s):  
P Schulz ◽  
C V Perrier ◽  
F Ferber-Perret ◽  
W J A VandenHeuvel ◽  
S L Steelman
Keyword(s):  
Single Dose ◽  
Urinary Excretion ◽  
Acetylsalicylic Acid ◽  
Blood Levels ◽  
Concomitant Therapy ◽  
Significant Drop ◽  
Acid Therapy ◽  
Prostaglandin Inhibitor ◽  
Clinically Significant ◽  
Higher Doses

Intermittent and concomitant acetylsalicylic acid (ASA) therapy was superimposed onto a 21-day regimen with diflunisal 250 mg b.i.d. Low doses of ASA (600 mg single dose or 300 mg q.i.d.) did not influence significantly diflunisal blood levels whereas a 600 mg q.i.d. dosing caused a small significant drop, especially at trough level. This drop is not expected to be clinically significant. No ototoxicity could be demonstrated with any treatment of diflunisal though four of fourteen subjects reported mild tinnitus during concomitant therapy at the higher doses of ASA. Diflunisal at 375 mg b.i.d. failed to alter the metabolism of a single dose of labelled ASA (600 mg) as judged by plasma levels, urinary excretion and plasma binding. Daily urinary excretion of prostaglandins E1 and E2 major metabolite was decreased by about 70% by diflunisal.

scholarly journals Nitrogen balance in adult female mink (Mustela vison) in response to normal feeding andshort-term fasting

1997 ◽  
Vol 78 (1) ◽  
pp. 83-96 ◽  
Author(s):  
Anne-Helene Tauson ◽  
Jan Elnif ◽  
Søren Wamberg
Keyword(s):  
Urinary Excretion ◽  
Renal Clearance ◽  
Adult Female ◽  
Accurate Determination ◽  
Mustela Vison ◽  
Published Data ◽  
Purine Derivatives ◽  
Total N ◽  
Creatinine Excretion

Ten adult female mink (Mustela vison) were studied in a 7 d balance experiment consisting of a 2 d pre-surgery feeding period, followed by surgery, 1 d of recovery, 4 d of ad libitum feeding, and a 2d fasting period. In this experiment (Expt A) the animals had osmoticpumps implanted for continuous release of radioactively-labelled p–aminohippuric acid (p–aminobenzoyl-2-[3H]glycine; [3H]PAH;n10) and 14C-labelled inulin ([14C]IN; n 5). Repeated 24 h collections of urine, corrected to 100%[3H]PAH or [14C]IN recovery, were used for accurate determination of N balances, 24 h urinary excretion of urea, creatinine, and total N, and calculation of mean 24 h renal clearance rates for endogenous creatinine and inulin. N balances were slightly below zero, but not significantly different between feeding and fasting periods, indicating that correction to 100% [3H]PAH recovery resulted in slight overestimation of thefinal balances. During fasting, withdrawal of the dietary water and protein loads resulted in a dramatic decline in 24 h urinary volume, and urea and creatinine excretion. Large individualvariations in 24h urinary creatinine excretion (with relative variation coefficients up to 30%) confirmed that this is an unreliable index of the completeness of urine collection. In this respect, recovery rates of [3H]PAH proved far more consistent. Renal clearance values obtained in fed mink were in fair agreement with published data from cats, dogs and ferrets (Mustela putorius furo). Inulin clearance was about 30% higher than endogenous creatinine clearance, although its decline in response to fasting was not significant. In a separate study (Expt B)another ten female mink were equipped with osmotic pumps containing [3H]PAH for determination of 24 h excretion rates of purine derivatives. During feeding, allantoin accounted for more than 97 % of the excretion of purine derivatives in urine, uric acid making up less than 2·5%, xanthine and hypoxanthine less than 1 %. In fasted animals, urinary excretion of each of these purine derivatives declined to less than 50% of the feeding value. In conclusion, an experimental technique is presented for efficient and accurate measurements of daily urinary excretion of nitrogenous constituents, which allows for correct determination of N balances in adult mink and, presumably, in other mammalian species.

Increased Fibrinogen Levels and Hemostatic Abnormalities in Patients with Arteriolar Nephrosclerosis: Association with Cardiovascular Events

2000 ◽  
Vol 84 (10) ◽  
pp. 565-570 ◽  
Author(s):  
Laura Zingaro ◽  
Cristiana Catena ◽  
Sergio De Marchi ◽  
Leonardo Sechi
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Normal Renal Function ◽  
Cardiovascular Events ◽  
Plasma Fibrinogen ◽  
Atherosclerotic Disease ◽  
Prothrombotic State ◽  
Arteriolar Nephrosclerosis ◽  
D Dimer

SummaryIncreased plasma fibrinogen levels and hemostatic abnormalities suggestive of a prothrombotic state are present in patients with endstage renal failure and could contribute to increased cardiovascular morbidity in these patients. We investigated the relationship between abnormalities of the hemostatic system and the degree of renal failure and whether these abnormalities are associated with increased prevalence of cardiovascular events in patients with arteriolar nephrosclerosis. In 425 patients recruited at a hypertension clinic we assessed the renal function by creatinine clearance, urinary protein excretion, and microalbuminuria, the prevalence of atherosclerotic disease, and measured prothrombin time, activated partial thromboplastin time, fibrinogen, prothrombin fragment 1+2 (F1+2), D-dimer, and antithrombin. Early impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) caused by arteriolar nephrosclerosis was found in 172 patients. Patients with early renal failure were significanly older and had significantly greater values of blood pressure, plasma fibrinogen, F1+2, and D-dimer than patients with normal renal function. Elevated D-dimer and fibrinogen levels were independently associated with the presence of decreased creatinine clearance. Log fibrinogen, log F1+2, and log D-dimer were inversely correlated with creatinine clearance. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was significantly greater in patients with mild renal failure than in those with normal renal function. Elevated levels of fibrinogen and D-dimer were associated with the presence of atherosclerotic disease independent of renal function and other risk factors. In conclusion, changes in hemostatic parameters occur early in the course of renal failure in patients with arteriolar nephrosclerosis, suggesting a prothrombotic state that may contribute to the risk for atherosclerotic disease at all levels of renal function.

Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin.

1986 ◽  
Vol 4 (9) ◽  
pp. 1392-1398 ◽  
Author(s):  
P A Reece ◽  
I Stafford ◽  
J Russell ◽  
P G Gill
Keyword(s):  
Renal Function ◽  
Urinary Excretion ◽  
Creatinine Clearance ◽  
Proximal Tubule ◽  
Antitumor Effect ◽  
Area Under The Curve ◽  
Renal Elimination ◽  
Median Increase ◽  
Urinary Levels ◽  
Ultrafilterable Platinum

Ultrafilterable plasma and urinary levels of platinum were quantitated for 24 hours after the first- and fourth-course infusion of cisplatin (CDDP) to seven patients. Four patients received 80 mg/m2 and three patients received 100 mg/m2 CDDP as a 2-hour infusion. The area under the curve (AUC) of ultrafilterable platinum, average renal clearance (CIR) of ultrafilterable platinum, and percentage of the platinum dose excreted in urine (% E) were determined for each infusion over the 26-hour period of the study. The AUC was higher in all patients after the fourth-course infusion, with a median increase of 74%. The median CLR was 494 mL/min (range, 214 to 996 mL/min) for the first course and decreased to 156 mL/min (range, 108 to 271 mL/min) for the fourth-course infusion (P less than .02). The median % E was 29.2% (range, 19.6% to 37.7%) for the first course and decreased to 19.9% (range, 12.4% to 25.9%) for the fourth-course infusion (P less than .02). There was no difference in creatinine clearance for the two infusions (median, 94 mL/min; P greater than .05). Urinary excretion of B2-microglobulin (B2-MG) and N-acetyl-B-glucosaminidase (NAG) was highly variable between patients and did not provide a useful predictor of changes in renal function. Four courses of CDDP therapy resulted in significantly reduced renal elimination of platinum in patients, probably through a reduction in the secretion of the drug in the proximal tubule of the kidney. The results suggest that increased antitumor effect and toxicity could occur in patients receiving sequential courses of cisplatin.

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