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Biomedical subjects

S Pancorbo

Publications and source records attributed to S Pancorbo.

At least 19 recordsLinked to original sources
PubMed1988

Variability in theophylline volume of distribution and clearance in patients with acute respiratory failure requiring mechanical ventilation.

This study examines the intrasubject variability in theophylline volume of distribution (V) and clearance (CL) in critically ill, mechanically ventilated adults. Fifteen patients received two intravenous doses of theophylline approximately ten hours apart. Although there was no statistical difference between the mean VI (first dose, 0.51 L/kg) and V2 (second dose, 0.47 L/kg), the absolute difference between measurements of 0.15 L/kg was statistically significant (p less than .05). Range of differences follows: between VI and V2, 3.8 to 72.4 percent (mean, 33.5 percent); between CL1 and CL2, 6.1 to 100 percent (mean, 32.2 percent). Absolute difference between clearances was 0.019 L/kg/hr. A comparative error analysis revealed an absolute difference for V of 27.9 percent and for CL of 37 percent. Considerable intra-subject variability was shown for theophylline V and CL in these critically ill adults. Variability in V was not significantly different than variability in CL, and may result in severe underdosing or overdosing.

Acute Disease↗
PubMed1988

Comparison of serum sampling methods for determining vancomycin dosage regimens.

The predictive ability of a four-point sampling method versus a two-point sampling method for vancomycin was assessed in 11 patients with various staphylococcal infections. All steady-state predictions were based on first-dose pharmacokinetic parameters. The mean vancomycin serum concentrations achieved at 4 and 8 h postinfusion were not significantly different from the predicted concentrations derived from either the four- or two-point method. Also, there was no significant difference between the two methods in predictive ability or accuracy. Both methods underpredicted the steady-state concentration to the same degree, 2.9 micrograms/ml at 4 h and 3.1 micrograms/ml at 8 h, which would appear to be clinically acceptable. A one-compartment pharmacokinetic model, which uses two serum concentrations, appears to be adequate for adjusting vancomycin regimens.

Adult↗
PubMed1987

Report of a survey of PharmD curricula: implications for accreditation standards.

The curriculum content of Doctor of Pharmacy Programs throughout the United States was evaluated with the objective of describing the set of standards now held by each school. A questionnaire was mailed to 40 Colleges of Pharmacy offering the PharmD Degree requesting curricula information. The mean total number of hours of instruction for pathophysiology and therapeutics was 27.1 hours, (range 62-1175). The largest section taught was cardiology (mean 38.9 hours), followed by infectious diseases (25.7), endocrinology (22.9), nephrology (22.5), and neurology (20.5). Courses in pharmacokinetics, statistics, and drug information were required by a majority of the programs. Clinical rotations in internal medicine, drug information, and ambulatory care were similarly required. There was considerable variation in the curricular requirements among the programs.

Accreditation↗
PubMed1987

Evaluation of gentamicin premixed admixtures: cost and clinical utility.

An objective of this study was to evaluate the cost effectiveness of employing gentamicin premixed admixtures compared to using exact, individualized compounded doses. Gentamicin use and waste data were collected over a 2-month period. Annualized institutional savings (300 beds) were projected to be $8,802. A second objective was to compare predicted to measured peak and trough serum gentamicin concentrations when premixed admixtures are used (rounding off computer generated doses to the nearest 10 mg) and when individually compounded exact doses are delivered. Twenty adults were randomized to receive premixed or compounded doses. Blood levels drawn at steady state were compared to predicted levels for the delivered dose. Differences between measured and predicted levels were not significant by performance of an independent t test on the mean square prediction errors. We conclude that it is cost effective and clinically valid to employ premixed intravenous admixtures in a large teaching hospital.

Adult↗
PubMed1986

Evaluation of the effect of variability in the volume of distribution of theophylline on the predictability of the iterative and the Chiou methods using computer simulations.

The effect of variations in the volume of distribution on the precision of the ability of two methods--the Chiou and the iterative--to predict the total body clearance (TBC) of theophylline was evaluated utilizing computer simulations. Pharmacokinetic data [volume of distributions (V), elimination constants (k)] measured in a group of 55 adult bronchitic patients were utilized to conduct the simulations. An average V of 0.45 L/kg was utilized to calculate TBC with the Chiou and the iterative methods. Separate simulations were conducted utilizing initial (C1) serum concentrations of 2 and 10 micrograms/ml. At the C1 = 2 micrograms/ml condition, the iterative method was statistically significantly more precise (mean squared prediction error, 379.5 vs. 508.5). There were no differences when the initial serum concentration was 10 micrograms/ml under the simulated conditions. At the lower initial condition (C1 = 2) the mean prediction error was 62.3 and 54.9% for the Chiou and the iterative methods, respectively, and it ranged from 0 to 477%. It is recommended that caution be utilized when theophylline doses are individualized using these methods.

Adult↗
PubMed1986

Evaluation of premixed intravenous theophylline loading doses.

We evaluated the use of a standard protocol utilizing premixed theophylline containers in comparison to traditional intravenous aminophylline loading doses in 19 critically ill adults. Blood samples were obtained immediately before and after 30-minute infusions of aminophylline and theophylline bags. Aminophylline loading doses were calculated to the exact mg/kg and were delivered as such. Calculation of the theophylline loading dose used a simplified protocol that uses doses rounded to the nearest 100 mg. Comparison of the relative performance of the two loading dose methods was evaluated by computing mean squared prediction errors and root mean squared errors. The two methods were not statistically different when evaluated by a matched pair t-test. We conclude that use of a standard protocol that rounds theophylline doses to the nearest 100mg results in peak theophylline concentrations not significantly different from those predicted.

Aged↗
PubMed1984

Cimetidine dynamics after repeated intravenous injection.

Cimetidine dynamics were studied in six multiple-trauma patients receiving 300 to 600 mg every 6 hr for prevention of stress ulceration. Patients received cimetidine intravenously for a mean duration of 7.8 days. There was a positive correlation between cimetidine serum concentration and gastric pH; the correlation between intragastric cimetidine concentration and gastric pH was stronger. The association between therapeutic efficacy (pH greater than 4) and serum concentration over 1 mcg/ml was significant. The association with gastric cimetidine concentration above 2 mcg/ml was significant.

Adult↗
PubMed1983

Evaluation of the effect of nonlinear kinetics on dosage adjustments of theophylline.

The pharmacokinetics of theophylline at two different dosage levels were studied in six adult volunteers. The subjects were allowed to reach steady-state serum concentrations of theophylline after 7 days of administration of a sustained-release oral product. There was a statistically significant decrease (p = 0.03) in the total body clearance (TBC) of theophylline at the higher dosage level. At a daily dose of 10.6 mg/kg/day, the mean TBC was 0.76 ml/min/kg, whereas at a dose of 15.7 mg/kg/day the TBC averaged 0.68 ml/min/kg. For two of the subjects, a linear increase in serum concentrations occurred with increasing doses. The remaining four subjects showed a saturation of the elimination processes at the higher dosage. The apparent maximum velocity (Vmax) calculated in these subjects averaged 2,923 mg/day. The mean Michaelis-Menten constant (Km) was 23.70 micrograms/ml. Computer-generated serum concentrations produced by a linear increase in doses predicted toxic concentrations of theophylline in two of the six subjects. The results suggest caution in employing a linear model for the individualization of theophylline therapy.

Administration, Oral↗
PubMed1983

A comparative study of netilmicin-cefoxitin and gentamicin-cefoxitin in surgical patients with serious systemic infection.

A double-blind, randomized study of gentamicin and netilmicin, each in combination with cefoxitin, was done to compare their respective efficacy and toxicity in patients with serious systemic infection. Thirty-seven surgical patients were evaluated for efficacy and 46 patients were evaluated for toxicity. The most frequently cultured organisms were Escherichia coli (15), Klebsiella sp (9), Proteus sp (6), and Bacteroides sp (4). For 23 patients treated with gentamicin-cefoxitin (G-C), the clinical response was favorable in 20/21 (95.2%) evaluable cases, and elimination or marked reduction of 33/34 (97.1%) organisms was achieved. For 14 patients treated with netilmicin-cefoxitin (N-C), the clinical response was favorable in 13/13 (100%) evaluable cases, and 19/20 (95%) organisms were eliminated or markedly reduced. Nephrotoxicity was defined as an increase in serum creatinine to greater than 25% over baseline with an absolute rise of at least 0.5 mg/100 ml to a value greater than or equal to 1.3 mg/100 ml. Based on these criteria, nephrotoxicity was seen in 2/27 (7.4%) patients treated with G-C and in 3/19 (15.8%) patients treated with N-C. Ototoxicity was defined as a greater than 20 dB loss at any frequency. Based on these criteria, ototoxicity was seen in 5/27 (18.5%) patients treated with G-C and 2/19 (10.5%) patients treated with N-C. The data show no significant difference in toxicity and suggest that netilmicin and gentamicin are both highly effective in combination with cefoxitin in patients who have serious infections after surgery.

Adolescent↗
PubMed1982

Cimetidine dynamics after single intravenous doses.

Cimetidine dynamics were studied in nine multiple-trauma patients. Mean elimination half-life was 2.27 hr, mean volume of the central compartment was 0.29 l/kg, mean volume at steady state averaged 0.90 l/kg, and mean total body clearance was 9.02 ml/min/kg. After intravenous cimetidine, drug concentrated in gastric fluid reached a peak concentration in 3 hr. Gastric plasma cimetidine ratios after equilibration ranged between 3.0 and 4.3. There was a correlation between cimetidine gastric juice concentration and gastric pH (r = 0.50), but no correlation was found between plasma cimetidine concentration and pH (r = 0.13).

Adult↗
PubMed1982

Peritoneal transport of vancomycin in 4 patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of vancomycin have been studied in 4 chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis. Patients received 1 g of vancomycin in 2 liters of dialysate during an initial phase, and serum and dialysate samples were collected for vancomycin determination. 54% of the amount introduced into the peritoneal cavity were absorbed systemically during a 6-hour cycle. Peak serum concentrations averaged 23.7 microgram/ml. Mean elimination half-life was calculated to be 66.9 h, and dialysis clearance averaged 2.4 ml/min.

Adult↗
PubMed1981

Pharmacokinetics of gentamicin in patients undergoing continuous ambulatory peritoneal dialysis.

Teh pharmacokinetics of gentamicin were studied in seven chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis. Patients received 100 mg of gentamicin in 2 liters of dialysate during an initial pass, and serum and dialysate samples were collected for gentamicin determination. Approximately 49% of the amount introduced into the peritoneal cavity was absorbed systemically during a 6-h cycle. Subsequent clearance of gentamicin from the serum occurred slowly with an elimination half-life of 36 h. Dialysis clearance of gentamicin during continuous ambulatory peritoneal dialysis was 2.94 ml/min.

Adult↗
PubMed1981

Quinidine pharmacokinetics in continuous ambulatory peritoneal dialysis.

The clearance of quinidine was evaluated in a patient undergoing continuous ambulatory peritoneal dialysis (CAPD). The dialysis clearance of quinidine was 0.793 ml/min which represented only 0.61% of the total body clearance (154.21 ml/min) of the drug. The elimination half-life of quinidine was 5.44 hours. Based on our results, dosage adjustment of quinidine does not appear to be necessary for patients undergoing CAPD.

Arrhythmias, Cardiac↗
PubMed1981

Pharmacokinetics of epsilon-aminocaproic acid during peritoneal dialysis.

Two patients requiring peritoneal dialysis were treated with epsilon-aminocaproic acid (EACA), an antifibrinolytic agent. Samples of serum and dialysate were assayed for EACA concentrations. Total body clearance, dialysis clearance, EACA half-life, and volume of distribution of EACA were calculated. Total body clearance of EACA was 26 ml/min, which is 25% of the drug clearance in patients with normal renal function. Our results suggest that patients undergoing peritoneal dialysis should receive 25% of the usual recommended dose of EACA. Dialysis clearance accounted for only 58% of total body clearance, suggesting an alternative route of elimination of EACA.

Aminocaproates↗
PubMed1981

Use of a pharmacokinetic method for establishing doses of aminophylline to treat acute bronchospasm.

A pharmacokinetic method of establishing individualized doses of aminophylline in patients with acute bronchospasm was evaluated. Patients admitted to a hospital who required intravenous aminophylline for bronchodilation were studied. Blood samples were drawn before treatment for theophylline-content measurement. Loading doses were administered intravenously and half-lives and volumes of distribution were determined. Individualized constant-rate infusions based on pharmacokinetic data were then begun. Heart rate, nausea, vomiting, seizures, and serum theophylline content were monitored during the study. The mean age of the 55 patients in the study was 54.3 years (range: 7 to 87). Patients with congestive heart failure or liver disease numbered 32; 30 patients were smokers. At approximately 24 hours after the calculated constant-rate infusion was begun, 85% of the patients had therapeutic serum levels of theophylline; 11% of the patients had subtherapeutic levels and 4% had toxic levels. All measured concentrations were between 7.5 and 23.0 microgram/ml. The study method produced significantly more patients in the therapeutic range than would have occurred if previously reported standardized methods had been used (p less than 0.05). Most patients had a decreased heart rate after treatment. No other adverse effects occurred that were attributable to i.v. aminophylline. It is concluded that, for patients in acute bronchospasm, individualizing i.v. aminophylline doses with patient-specific pharmacokinetic data can increase significantly the number of patients who rapidly attain therapeutic serum theophylline levels.

Acute Disease↗
PubMed1980

Prediction of serum gentamicin concentrations in patients undergoing hemodialysis.

The predictability of a one-compartment pharmacokinetic model for estimating serum gentamicin concentrations in patients undergoing hemodialysis was studied. Nine hemodialysis patients with gram-negative bacillary infections requiring aminoglycoside therapy and with creatinine clearances of less than 1 ml/min were studied. A series of blood samples was assayed by radioimmunoassay to determine serum concentrations after an initial 1.5- to 2.0-mg/kg i.v. dose and throughout the dialysis period. These data were used to predict post-dialysis serum concentrations and post-dialysis doses needed to achieve therapeutic concentrations. The mean apparent volume of distribution for gentamicin was 0.26 +/- 0.06 liter/kg. The mean gentamicin half-life was 31.5 hours before dialysis and 7.6 hours during dialysis. No significant differences were found between predicted and measured peak gentamicin serum concentrations after dialysis; nor were there significant differences for peak serum concentrations obtained with a post-dialysis gentamicin dose (p less than 0.001). Neither the peaks predicted based on the individual patient's pharmacokinetic values nor those based on the average of the patients' pharmcokinetic values were statistically different from measured. The kinetic model developed can be used to determine gentamicin dosing for hemodialysis patients and to determine an average elimination rate constant for a given dialysis apparatus.

Adult↗