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Biomedical subjects

C C Peck

Publications and source records attributed to C C Peck.

At least 55 records · Page 3Linked to original sources
PubMed1989

Clinical utility of a Bayesian dosing program for phenytoin.

We performed two studies to assess the clinical utility of a Bayesian regression analysis computer program for phenytoin (PHT). In a randomized prospective study of 40 epileptic patients, the dosing program was significantly more accurate (p = 0.002) and less biased (p = 0.02) than a group of physicians at hitting a target PHT serum-concentration. Initial serum PHT concentrations that were not steady state were associated with the largest dosing errors by physicians but did not affect the accuracy of the dosing program. In a second study, we used the dosing program to predict 91 serum concentrations in 31 patients with PHT toxicity after the drug was stopped (initial concentration 26-69 micrograms/ml). The program predicted serum concentrations with a mean error of 3.49 +/- 0.29 micrograms/ml without significant tendency to over- or underpredict. We conclude that this dosing program may aid clinicians by improving dosing accuracy and predicting serum concentrations in patients with PHT toxicity.

Adolescent↗
PubMed1989

Pharmacokinetics of intravenous immunoglobulin in neonates.

Intravenous immunoglobulin (IVIG) may be a therapeutic adjunct to antibiotic treatment of neonatal infections. We examined the pharmacokinetics and safety of IVIG in human neonates. Thirty neonates with suspected sepsis were randomly assigned either to a treatment (receiving either 250, 500, or 1,000 mg/kg of IVIG plus antibiotics) or control (antibiotics alone) group. The 500 mg/kg dose produced a rise in total IgG for greater than 8 and in group B streptococcus (GBS) type-specific IgG for greater than 4-14 days. The type-specific antibody elevation varied with the amount of pathogen-specific antibody and dose of IVIG. Pharmacokinetic analysis suggests a Vdss of 42 ml/kg, Cl of 3.0 ml/kg/day, a biphasic elimination curve, and a terminal elimination half-life of 24.2 days. No toxicity was observed. These data may be valuable in determining optimal dosing schedules for IVIG in treating or preventing neonatal infections.

Anti-Bacterial Agents↗
PubMed1989

Transcutaneous collection of theophylline: constancy and linearity of skin permeability.

Transcutaneous chemical collection is a novel method for noninvasive collection and measurement of body exposure to chemicals using a transcutaneous collection device (TCD) consisting of a circular adhesive-tape-encased saline-activated carbon-aquagel patch. The objectives of this study were to determine (1) the time-course of skin permeability change after the placement of a TCD on the skin, and (2) the relationship between the amount of theophylline collected in a TCD and the amount of theophylline in the body as expressed by the area under the plasma concentration-time curve (AUC). Skin permeability changes were determined by emplacing TCDs (24/monkey) on the chests and abdomens of female rhesus monkeys (12 studies in 4 monkeys) at 48, 24, 6, 3 and 1 h prior to dosing with aminophylline (10 mg/kg of theophylline, i.v.) over 30 min. Several blood samples were collected, and TCDs were removed at 24 h post-dose; samples were assayed for theophylline by HPLC. The apparent permeability coefficients (Kp) increased following TCD placement reaching 90% of maximum by 17 h. The relationship between the amount of theophylline collected in the device (Q) and amount in the body over time was determined by emplacing TCDs on rhesus monkeys (8 studies in 4 monkeys) 24 h prior to administration of 10 mg/kg of theophylline. Qs from the TCDs removed at 0.17, 0.5, 1, 3, 6 and 24 h were linearly related to the plasma AUC according to the relationship: Q = (A x Kp) x AUC, where A is the area of gel in contact with the skin for each TCD.

Animals↗
PubMed1989

Bayesian regression analysis of non-steady-state phenytoin concentrations: evaluation of predictive performance.

Michaelis-Menten saturable pharmacokinetics confound the determination of appropriate phenytoin maintenance doses. This study retrospectively evaluated the performance of an IBM-PC/XT computer program applying Bayesian regression to the "explicit solution to the Michaelis-Menten equation." Zero to five non-steady-state phenytoin serum concentrations were used to predict either non-steady-state concentrations at least 10 days in the future (n = 49) or steady-state concentrations (n = 20). Non-steady-state concentration prediction precision (% mean absolute error) using 0-5 non-steady-state feedbacks was 137%, 62%, 39%, 31%, 25%, and 15%, respectively, and steady-state concentration prediction precision was 446%, 47%, 50%, 44%, 21%, and 13%, respectively. Elimination of subjects receiving concurrent drugs known to induce phenytoin metabolism significantly improved predictions based on population priors; however, performance improvements were not apparent after two serum level feedbacks. The program provided clinically acceptable predictions with four or more feedbacks. Refinement of population parameters and optimal sampling times should further improve performance.

Aged↗
PubMed1988

Outward transcutaneous chemical migration: implications for diagnostics and dosimetry.

Chemical substances migrate outwards from within the body to the skin surface by diffusion from cutaneous capillaries across the epidermis. Heretofore, study of transepidermal chemical emissions have been restricted to substances which are in the vapor phase at skin surface temperature. We have investigated outward transcutaneous chemical migration of nongaseous chemicals by devising an occlusive transcutaneous chemical collection system, consisting of a tape-encased plug of gelled saline in which activated carbon is dispersed. Investigations of nine chemicals in 'fuzzy' rats, rhesus monkeys, and man provide data which are consistent with a general theory of outward transcutaneous chemical migration. This noninvasive continuous transcutaneous sampling technique provides a new method for investigating skin permeability in vivo and may provide a basis for convenient diagnosis and monitoring of chemical exposure.

Animals↗
PubMed1988

Clinical assessment of a two-compartment Bayesian forecasting method for lidocaine.

The predictive performance of a two-compartment Bayesian forecasting method for lidocaine (L) was evaluated concurrently with lidocaine therapy in 46 hospitalized patients; 14 of these patients presented with congestive heart failure (CHF). Using an HP-85 microcomputer, demographic and dose-concentration information obtained during continuous lidocaine therapy was used to forecast subsequent lidocaine concentrations. One lidocaine concentration was obtained within each of the three intervals following initiation of lidocaine infusions: I1 (1-6 h), I2 (6-12 h), and I3 (greater than 12 h). Patients were categorized into 4 groups: (a) short-term infusions (less than 24 h) without CHF, (b) short-term infusions with CHF, (c) long-term infusions (greater than 24 h) without CHF, and (d) long-term infusions with CHF. The mean prediction errors (range -0.60-0.27) included zero (95% confidence limits) in all groups and suggested no bias. Forecasts of the I3 lidocaine concentrations were consistently more precise [lower mean absolute errors (MAE) and root mean squared errors] using the lidocaine concentration obtained during the 6-12-h interval (I2) than when the lidocaine concentration obtained at the earlier interval (I1) was used. The MAE was reduced by 20-40% when a single lidocaine concentration obtained during I2 was used as compared to I1. Precision was only slightly improved with the use of two lidocaine concentrations. We conclude that this Bayesian algorithm is unbiased and delivers acceptable precision in forecasting lidocaine concentrations.

Adult↗
PubMed1986

Tachykinin modulation of coronary blood flow.

In pentobarbital anesthetized, open chest pigs, coronary blood flow (CBF), myocardial contractility and systemic hemodynamic variables were monitored during intracoronary injections of substance P (SP), neurokinin A (NA) or neurokinin B (NB). SP was most potent in increasing CBF although NA was also active in high doses while NB had absolutely no effect. SP was also more potent than NA in producing systemic hypotension. The data suggests that SP and its receptors might be potentially important modulators of CBF.

Animals↗
PubMed1986

Evaluation of a Bayesian regression-analysis computer program for predicting phenytoin concentration.

A microcomputer program using Bayesian regression analysis to predict serum phenytoin concentrations was evaluated. Phenytoin concentration-time data from nine healthy male volunteers and one male patient were obtained from published studies. For two different dosage regimens that each subject received, the last available predose concentration on the sixth day of the regimen was predicted using observed predose concentrations on both the morning of the third day and on each of the first three days of phenytoin administration. In nine subjects who received at least 10 days of phenytoin therapy, observed concentrations after more than 10 days of therapy were predicted using both one and three observed serum concentrations. Also, in six subjects, the observed predose concentrations for the first three days of an initial phenytoin regimen were used to predict the last predose concentration observed during each subject's second regimen. Predictive performance of the program was evaluated using mean error (m.e.) as a measure of bias, mean absolute error (m.a.e.) as a measure of precision, and root mean square error (r.m.s.e.) as a composite measure of bias and precision. The majority of the predicted serum concentrations were accurate. Predictions of serum concentrations after six days and after more than 10 days of phenytoin therapy were somewhat more accurate when three serum concentrations were used than when only one concentration was used. In the six subjects for whom concentrations from an initial regimen were used to predict those in a second regimen, the largest prediction error was 5 mg/L (m.e. 0.88, m.a.e. 1.9, and r.m.s.e. 2.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Bayes Theorem↗
PubMed1986

Clinical pharmacokinetics: a simplified approach, Part 2.

Part 1 of this two-part series in clinical pharmacokinetics (J Natl Med Assoc 1985; 77:475-482) introduced the clinician to the basic principles required for rational therapeutic drug management at the bedside. Practical problems were included that demonstrated how these principles could be put to clinical use.In Part 2 the clinical pharmacology of three commonly used drugs (theophylline, digoxin and gentamicin) are discussed, and practical problems are presented to illustrate the use of their pharmacokinetic profiles.

Humans↗
PubMed1985

Disposition and bioavailability of various formulations of tetrahydrocannabinol in the rhesus monkey.

Oral delta 9-tetrahydrocannabinol (THC) in gelatin capsules is under evaluation as an antiemetic agent in cancer patients, but knowledge concerning its bioavailability is incomplete and, furthermore, alternative routes of administration may be desirable. In this study, the disposition of THC was determined in four rhesus monkeys given 2.5-mg/kg doses using the following routes of administration and formulations: intravenous (iv); orally (po) on a cookie and in gelatin capsules; intramuscularly (im) in Tween-80 and in Emulphor-EL620; rectally in various suppository bases. Serum THC concentrations were measured by RIA and analyzed by weighted nonlinear regression. Serum concentrations were best described by a sum of two exponentials with alpha and beta half-lives (mean +/- SD) of 0.74 +/- 0.59 and 14.9 +/- 12.5 h. Apparent bioavailability (%F +/- SD) of various formulations of THC were: gelatin capsules, 26 +/- 14; cookie, 89 +/- 16; intramuscularly in Tween-80 and in Emulphor, 39 +/- 13 and 102 +/- 15, respectively. Using the method of statistical moments, mean residence times in the body (h +/- SD) were: intravenous, 6.08 +/- 1.60; cookie, 21.92 +/- 3.11; gelatin capsule, 26.80 +/- 23.61; intramuscularly in Emulphor, 10.92 +/- 3.46 (in Tween-80, not calculated). THC was not bioavailable by the rectal route. We conclude from this study that THC formulated as a gelatin capsule exhibits a low and variable extent of bioavailability and that intramuscular THC may be a useful alternative route of administration since it is more completely bioavailable.

Administration, Oral↗
PubMed1985

Clinical pharmacodynamics of theophylline.

The clinical pharmacodynamics of theophylline, which concerns the correlation between the serum theophylline concentration ([TH]) attained during therapy for asthma and improved pulmonary function or unwanted side effects, serves to link the pharmacokinetics of theophylline with the time course of clinical outcome. Although the minimum effective and maximum safe [TH]s have been known for some years, it was only recently shown that maximal improvement in pulmonary function lags behind rapidly changing [TH]s and that improved pulmonary function relates to increasing [TH]s within the therapeutic range. While much is known about the determinants of theophylline disposition in patients with asthma, enabling individualized pharmacokinetically based therapy, it is difficult to predict the clinical pharmacodynamic outcome. Investigation of the effects of age, cardiopulmonary disease, concurrent drugs, diet, circadian rhythms, and other patient features on theophylline clinical pharmacodynamics may provide a basis for prediction of individual patient responsiveness to theophylline and lead to further optimization of theophylline therapy in asthma.

Asthma↗
PubMed1985

Hereditary warfarin resistance. Investigation of a rare phenomenon.

A 57-year-old black woman required a daily dosage of 50 mg of warfarin sodium to maintain her prothrombin time in a therapeutic range. The central volume of distribution and clearance of warfarin were normal for this patient. These findings, combined with the patient's requirement for plasma warfarin levels four times greater than those usually required to achieve adequate anticoagulation, indicated that the relative resistance was due to altered pharmacodynamics of warfarin. The only child of the propositus, a daughter, showed a similar relative resistance, confirming that this family is the third to be reported with hereditary resistance to warfarin.

Adult↗
PubMed1984

Extended least squares nonlinear regression: a possible solution to the "choice of weights" problem in analysis of individual pharmacokinetic data.

It is often difficult to specify weights for weighted least squares nonlinear regression analysis of pharmacokinetic data. Improper choice of weights may lead to inaccurate and/or imprecise estimates of pharmacokinetic parameters. Extended least squares nonlinear regression provides a possible solution to this problem by allowing the incorporation of a general parametric variance model. Weighted least squares and extended least squares analyses of data from a simulated pharmacokinetic experiment were compared. Weighted least squares analysis of the simulated data, using commonly used weighting schemes, yielded estimates of pharmacokinetic parameters that were significantly biased, whereas extended least squares estimates were unbiased. Extended least squares estimates were often significantly more precise than were weighted least squares estimates. It is suggested that extended least squares regression should be further investigated for individual pharmacokinetic data analysis.

Computers↗
PubMed1982

Applications of isotope differentiation for metabolic studies with di-(2-ethylhexyl) phthalate.

The pervasiveness of the plasticizer di-(2-ethylhexyl) phthalate (DEHP) in the environment and especially in the laboratory results in a background that may cause severe interference with analytical studies. Animal-to-animal variability in the distribution of DEHP metabolites in excreta normally makes it necessary to use large groups of animals when different treatments are compared. Finally, radioactive tracers are usually considered undesirable for metabolic studies involving human subjects. All of these problems can be overcome through the use of multiple isotopic labels, especially 12C/13C/14C. Examples are given involving rats and monkeys, and applicability to humans is discussed. The principles involved are not limited to any particular class of test compounds. In rats, the competing pathways for metabolism of phthalate esters produce a different distribution of metabolites from a small intravenous dose of DEHP than from a large oral dose.

Administration, Oral↗