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Biomedical subjects

J D Robinson

Publications and source records attributed to J D Robinson.

At least 91 records · Page 5Linked to original sources
PubMed1983

Effect of serum separator blood collection tubes on drug concentrations.

Using the EMIT assay, we tested clinical samples from patients receiving 12 commonly monitored drugs to evaluate the effect of serum separator gel contained in serum separator blood collection tubes (SST) (Becton-Dickinson). There were significant concentration decreases for lidocaine, pentobarbital, and phenytoin. In vitro experiments demonstrated that this effect on phenytoin was dependent on time of exposure to the gel and volume of whole blood, but was not dependent on the presence of red blood cells or initial concentration. Bias attributed to the use of SST could interfere with the usefulness of clinical results at the upper and lower limits of the therapeutic range. This problem can be minimized by processing samples of at least 2 ml within 1 h.

Blood Specimen Collection↗
PubMed1983

The effect of ibuprofen on serum digoxin concentrations.

This study was undertaken to determine the effects of ibuprofen (Motrin), in daily doses of at least 1600 mg, on steady-state digoxin concentrations. A total of 12 ambulatory patients (10, female; 2, male), with a mean age of 66 years (38-81 yr), completed the study. An initial baseline serum digoxin level was obtained, with follow-up levels at 7 days and, whenever possible, 28 days after ibuprofen initiation. Serum creatinine concentrations were not significantly different from baseline to 7 or 28 days of ibuprofen therapy. Results show a statistically significant (p less than 0.05) increase in digoxin levels after seven days of ibuprofen. The mean increase was 59 percent (range, 10.7-325.4 percent), with 10 of the 12 patients displaying increased seven-day levels. Digoxin levels drawn 28 days after ibuprofen initiation were not statistically different from baseline or seven-day digoxin levels.

Aged↗
PubMed1983

Metabolism of loprazolam in rat, dog and man in vivo.

The metabolism of 14C-loprazolam has been studied in rat, dog and man in vivo. In rat, the major metabolic pathways were hydroxylation on the benzodiazepine ring, and reduction and acetylation of the nitro group. Both metabolites were identified by co-chromatography with standards, and were present in urine and bile conjugated with glucuronic acid. In both dog and human urine and bile significant amounts of the piperazine-N-oxide were found. This N-oxide was identified by co-chromatography with authentic compound and by mass spectroscopy. Both loprazolam and the dog biliary metabolites were hydrolysed spontaneously to polar material. Neither treatment with beta-glucuronidase nor incubation with gut microflora had any further effect. Only polar metabolites were found in dog and human faeces. The principal non-polar material found in rat plasma was the diazepine-hydroxy compound, and little loprazolam was present. Significant levels of loprazolam and lower levels of an unidentified metabolite were found in ether extracts of dog and human plasma. Both the piperazine-N-oxide and loprazolam were found in similar quantities in chloroform extracts of human plasma, and at two hours after dosage, the N-oxide and loprazolam accounted for greater than 90% of the radioactivity present in the plasma.

Animals↗
PubMed1983

The absorption of intramuscular chlordiazepoxide (Librium) in patients with severe alcoholic liver disease.

Intramuscular chlordiazepoxide (CDX) is commonly administered to alcoholic liver disease (ALD) patients requiring prompt management of alcohol agitation, anxiety, and delirium tremors. Sedative action is associated with plasma levels of approximately 2.0 mcg/ml, however, intramuscular CDX has been shown to produce peak concentrations consistently below 2.0 mcg/ml in normal subjects. The present study was designed to define the absorption characteristics of intramuscular 25 mg CDX in males with ALD. Five normal males had mean CDX absorption half-lives of 3.0 h and peaked at 0.8 mcg/ml in 7.2 h, while 11 males with ALD had mean absorption half-lives of 9.0 h, and peaked at 0.7 mcg/ml in 19.1 h when they received the drug dissolved in normal saline. Four other males with ALD who received CDX dissolved in the manufacturer's diluent had significantly slower mean absorption half-lives of 16.1 h which peaked at 0.3 mcg/ml in 35.2 h. Significant linear correlations were found with age (r = 0.60, p less than 0.01), body weight (r = 0.55, p less than 0.01), and serum albumin (r = 0.60, p less than 0.01). Because of the extremely slow intramuscular absorption of CDX dissolved in normal saline or the manufacturer's diluent in males with ALD, we do not recommend this route of administration in this population.

Absorption↗
PubMed1983

Pharmaceutical services in family practice medical residency training programs.

The extent and nature of pharmacists' involvement in family practice medical residency training programs was assessed using a national survey. Department chairmen of all 386 approved family practice residency training programs in the United States were contacted and asked to provide the names and addresses of pharmacists in charge of pharmaceutical services in the centers. A 46-item, six-page questionnaire was mailed to each pharmacist with a follow-up mailing, then a telephone call, to nonresponders. Department chairmen of 68 (18%) of the programs reported having at least one pharmacist in the center. Responses to the questionnaire were obtained from 53 (78%) of the pharmacists, four of whom were no longer involved with family practice centers. Most of the remaining 49 pharmacists were men (76%) between 30 and 40 years old (59%) with an academic appointment (67%) and a doctor of pharmacy degree or some type of postgraduate training. Drug-distribution services were provided in 37% of the centers. All pharmacies offered clinical services. Almost all pharmacies (92%) offered educational services to both medical and nursing staffs, and pharmacists in 74% of the centers were involved in research. Few family practice medical residency training centers have pharmaceutical services conducted by a pharmacist; centers with pharmacists have a wide variety of distributive and clinical services.

Family Practice↗
PubMed1983

Determination of ideal body weight for drug dosage calculations.

Formulas for ideal body weight (IBW) in men and women were derived from the Metropolitan Life Insurance Company height and weight tables. Regression determinations of median weight versus height were performed for men and women. A program for a minicomputer was developed to generate plots for small, medium, and large frame sizes and for subjects of all frame sizes. Equations for ideal body weight were derived from the resulting data. For men of all frame sizes, IBW = 51.65 kg + 1.85 kg/inch of height greater than 5 feet. For women of all frame sizes, IBW = 48.67 kg + 1.65 kg/inch of height greater than 5 feet. More accurate estimates of IBW by frame size can be obtained using equations derived from the plots for men and women of each frame size. Estimates of IBW obtained by the widely used empirical method probably contain only minor errors. However, formulas derived from actual height and weight data should be used in pharmacokinetic determination of dosage regimens for some drugs.

Body Height↗
PubMed1982

Tryptic digestion of the (Na + K)-ATPase is both sensitive to and modifies K+ interactions with the enzyme.

Tryptic digestion of the (Na + K)-ATPase in the presence of choline chloride or NaCl ("Na-type") and in the presence of KCl ("K-type") produced distinct patterns of peptide fragments and losses of catalytic activity. The K0.5 for K+ to shift digestion from the Na-type, and its sensitivity to dimethyl sulfoxide and Triton X-100, were consistent with K+ acting at sites on the cytoplasmic face of the enzyme through which the K-phosphatase reaction also is activated. Reagents favoring the E1 conformational states, oligomycin, Triton, and ATP, shifted the pattern toward the Na-type, whereas those favoring E2 states, dimethyl sulfoxide, MgCl2, and MnCl2, shifted the pattern toward the K-type. Na-type digestion caused a greater loss of K-phosphatase than (Na + K)-ATPase activity, and the residual K-phosphatase activity was more sensitive to inhibition by Triton and ATP but stimulated more by dimethyl sulfoxide and inhibited less by Pi and MnCl2; all these effects are consistent with such digestion shifting equilibria toward E1 enzyme states. Accordingly, the K0.5 for K+ to activate the (Na + K)-ATPase was increased. However, the K0.5 for the K-phosphatase was unchanged; this observation requires revision of previous formulations, and bears on additional aspects of enzyme activity as well.

Animals↗
PubMed1982

Substrate interactions with brain (Ca + Mg)-ATPase.

ATP hydrolysis by a partially purified (Ca + Mg)-ATPase preparation from rat brain increased with substrate concentration in a biphasic fashion, with apparent Km values of 3 microM and 0.1 mM. Ca-dependent phosphorylation, however, had only a single Km value, 3 microM. KCl increased ATPase activity in both concentration ranges, but the K0.5 for KCl decreased from 7 mM to 0.3 mM as the ATP concentration was reduced from 1 mM to 10 microM. The K0.5 for MgCl2 decreased somewhat less, from 3 mM to 0.6 mM with ATP concentrations from 1 mM to 1 microM, but was far lower for steady-state phosphorylation, 0.03 mM. (Ca + Mg)-dependent hydrolysis was not demonstrable with other nucleotide triphosphates or p-nitrophenyl phosphate, and these substances, as well as a reaction product, Pi, were also inhibitors. On the other hand, ADP inhibited at both ATP concentration ranges, and also stimulated dephosphorylation. This pattern of responses to substrate and cations is reminiscent of that of well-characterized transport ATPases, suggesting similar roles and mechanisms.

Adenosine Diphosphate↗
PubMed1982

Optimal lidocaine dosing in patients with myocardial infarction.

A decrease in hepatic clearance and volume of distribution in patients with congestive heart failure frequently leads to toxicity when drugs such as lidocaine are administered. To determine the effect of adjusted dosing of lidocaine in patients with myocardial infarction, we studied 32 patients receiving lidocaine either by a conventional method (control group: 1-2 mg/kg bolus, then 1 to 4 mg/min) or by an adjusted regimen based on the presence or absence of heart failure [experimental group: 1-2 mg/kg bolus; then, class I (no heart failure), 35 to 88 micrograms/kg/min; class II (heart failure), 12 to 35 micrograms/kg/min]. Plasma lidocaine levels were determined at 2 and 5 h of the infusion by enzyme multiplied immunoassay technique (EMIT) and gas liquid chromatography (GLC). Ten of 33 determinations in the control group were in the toxic range, i.e., greater than 6 micrograms/ml, and four others were subtherapeutic, i.e., less than 2 micrograms/ml. In contrast, 13 of 16 determinations in the experimental group were in the therapeutic range, and none were in the toxic range. These data show that administration of lidocaine by a conventional method may produce diverse plasma levels that may occasionally be in the toxic range. Modified dosing based on cardiac status may result in optimal levels in most patients.

Adult↗
PubMed1982

EMIT theophylline assay at reduced cost.

An experiment was designed to determine if a new EMIT theophylline method that reduces reagent costs can maintain the standard EMIT method's high degree of accuracy and precision. Eight known theophylline concentrations ranging from 1.5 to 75 micrograms/ml were analyzed by both methods. Two hundred five assays were performed on study patients using the new method. During 4 months of clinical service, 51 assays, ranging from 0 to 51 micrograms/ml, were performed by the standard method, and during the following 12 months 213 clinical service assays, ranging from 0 to 35.6 micrograms/ml, were performed by the new method. A strong correlation (r = 0.997) was demonstrated between the new and standard EMIT methods. Both methods had similar variance and curve stability. A 56% reduction in reagent expenses was realized with the new method over a 12-month period.

Adult↗
PubMed1982

Influence of cimetidine on oral diazepam elimination with measurement of subsequent cognitive change.

In a double-blind crossover design, the effect of cimetidine on oral diazepam pharmacokinetics and an evaluation of cognitive function change was studied in seven healthy volunteers. Subjects randomly received placebo or cimetidine 300 mg orally every 6 h for a total of five doses prior to diazepam 10 mg. A significant increase in diazepam elimination half-life from (mean +/- s.e. mean) 66.9 +/- 21.4 to 89.6 +/- 22.5 h (P = 0.006) and area under the plasma concentration-time curve from 5.06 +/- 1.47 to 8.93 +/- 1.88 micrograms ml-1 h (P = 0.028) was observed indicating a probable cimetidine induced inhibition of diazepam hepatic metabolism. Digit symbol substitution and visual analogue scales were used to measure the effect of an alteration of diazepam kinetics on cognitive function. An enhancement of pharmacological effect as reflected in digit symbol substitution scores and visual analogue scale measurements was not observed.

Administration, Oral↗
PubMed1982

Computer-simulated conversion from intravenous to sustained-release oral theophylline.

A computer equipped with a pharmacokinetic program was used to theoretically determine the proper time to administer the first dose of a commonly prescribed, sustained-release oral theophylline product (Theo-Dur) in patients maintained on a continuous intravenous aminophylline infusion. Four conversion methods were tested. They included giving the first oral dose (1) immediately upon discontinuation of the iv infusion, (2) two hours after discontinuing the iv infusion, (3) four hours after discontinuing the iv infusion, and (4) two hours before discontinuing the iv infusion. Each of the four methods was simulated in three groups of patients: smokers, nonsmokers, and patients with cirrhosis. Results showed that, in most situations, given the first oral dose immediately upon discontinuation of the intravenous infusion provided minimal deviation from eventual steady-state levels. In addition, this computer simulation suggests that the initial 12-hour maintenance dose recommended by the FDA may result in toxicity in certain patient groups.

Administration, Oral↗
PubMed1982

A comparison of various types of patient instruction in the proper administration of metered inhalers.

The administration technique employed by 42 inpatients using metered inhalers were observed. Proper performance of the six steps recommended by the manufacturer provided the guidelines for correct administration. The degree of compliance with proper technique was defined as the number of steps correctly executed by the patient. The mean number of steps correctly performed was 2.9 out of the possible six (48.3 percent). Twenty-four patients were then randomized into one of three groups. Group I received the manufacturer's instruction sheet, Group 2 received counseling from a pharmacist, and Group 3 received both the manufacturer's instruction sheet and counseling from a pharmacist. There was a significant improvement in the postinstruction technique in Groups 2 and 3, while Groups 1 failed to demonstrate any significant improvement. Comparisons were then made among the three groups. No significant difference was found between Group 2 and Group 3. However, both Groups 2 and 3 were found to be significantly different (p less than 0.05) from Group 1. This study shows that pharmacist counseling can significantly improve the degree of patient compliance in the administration of metered inhalers.

Aerosols↗