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Biomedical subjects

C H Nightingale

Publications and source records attributed to C H Nightingale.

At least 199 records · Page 11Linked to original sources
PubMed1984

Pharmacokinetics of trimethoprim and sulfamethoxazole in serum and cerebrospinal fluid of adult patients with normal meninges.

The pharmacokinetics of trimethoprim (TMP) and sulfamethoxazole (SMX) in cerebrospinal fluid (CSF) and serum after a single intravenous infusion of 5 mg of TMP and 25 mg of SMX per kg of body weight over approximately 120 min were studied i nine patients who had uninflamed meninges and were undergoing elective myelography. Peak concentrations of TMP and SMX in CSF were 1 microgram/ml and 13.8 micrograms/ml, respectively. The peak TMP concentration in CSF occurred significantly earlier than the peak SMX concentration (60 versus 480 min postinfusion). At 15 h, there was no detectable TMP in the CSF, and there was 4.7 micrograms of SMX per ml of CSF. In the postdistribution phase (in CSF), simultaneous CSF-to-serum concentration ratios ranged from 0.23 to 0.53 for TMP and from 0.20 to 0.36 for SMX. CSF penetration (measured by comparison of the area under the curve of the composite CSF and serum concentration-time curves) was 18% for TMP and 12% for SMX. A loading dose of TMP-SMX (bases on TMP) of 10 to 12 mg/kg and a maintenance dose of 6 mg/kg every 8 h or 8 mg/kg every 12 h (with a 2-h infusion) should yield steady-state peak concentrations of at least 5 micrograms of TMP per ml of serum and 160 micrograms of SMX per ml of serum. Further studies of TMP-SMX administered in these doses in the treatment of serious bacterial infection, including meningitis, are warranted.

Adult↗
PubMed1984

Comparative pharmacokinetics of cefotaxime and ceftizoxime and the role of desacetylcefotaxime in the antibacterial activity of cefotaxime.

A single 15 mg/kg i.v. dose of cefotaxime (CTX) and ceftizoxime (CTZ) were given to six adult volunteers on two separate occasions in a cross-over experiment to determine the pharmacokinetics of each drug and the desacetyl metabolite of cefotaxime, desacetylcefotaxime (des-CTX). From these data, mock serum samples were prepared in human serum to simulate the concentrations of CTX, CTZ, and des-CTX at the following times postdose: 5, 10, 30, and 45 min; 1, 1.5, 2, 3, 4, 5, 6, 8, and 10 hr. At each of these time periods, serum bacteriostatic and bactericidal assays were performed against selected pathogens (Escherichia coli, Serratia marcescens, Enterobacter species) with similar susceptibilities to CTX and CTZ, but with varying sensitivity to des-CTX, and against one organism (Bacteroides fragilis) toward which CTX and des-CTX exhibited synergistic activity. From these studies, it was found that des-CTX can appreciably lengthen the microbiologic action of CTX when it has a high degree of inherent activity (MIC less than or equal to mcg/ml) against the organism, or when it behaves synergistically with CTX toward the bacterium, or both. It is possible that the major advance of CTX and CTZ pertains to their ability to kill many organisms at extremely low concentrations, allowing for monotherapy with low and infrequent dosing, which is very cost-effective in comparison with high and more frequent dosing required by older agents or with antibiotic combinations.

Adult↗
PubMed1984

Prophylaxis of oral candidiasis with clotrimazole troches.

Oropharyngeal candidiasis is frequently a complication of patients with altered immune states. Clotrimazole troches are effective in the treatment of Candida and were evaluated in this study in a prophylaxis regimen. Patients with malignant neoplasms who were receiving chemotherapy and renal transplant recipients who were receiving immunosuppressives were randomized to receive either clotrimazole (10 mg) or placebo troches three times a day in a prospective, double-blinded study. Eighty-four patients were randomized into the study, 18 patients with leukemia, 19 patients with malignant neoplasms, and 47 patients with renal transplants. Among all patients, thrush developed in 57% while receiving placebo compared with 13% while receiving clotrimazole prophylaxis. Prophylaxis showed significant benefit for the renal transplant recipients and for patients with solid malignant neoplasms, but not for the leukemic patients. Clotrimazole troches are effective in preventing oral candidiasis in a select group of patients.

Administration, Oral↗
PubMed1984

Applying for a certificate of need for unit dose and i.v. admixture services in a Connecticut hospital.

The process of obtaining regulatory-agency review of a proposal for unit dose and i.v. admixture services is described. In a 901-bed community hospital in Connecticut, a pharmacy department proposal for instituting unit dose distribution and expanding the i.v. admixture service was supported by the hospital administration and included in hospital budget projections. A state body that regulates hospital revenues, the Commission on Hospitals and Health Care (CHHC), rejected the proposal for these changes in pharmaceutical services. The pharmacy and hospital administration subsequently petitioned the Health Systems Agency in that jurisdiction for a certificate of need (CON); the procedure required that the application also be simultaneously submitted to CHHC. Implementation of the program over a three-year period was proposed. The CON application was submitted in July 1981; it required detailed information from pharmacy, nursing services, and hospital administration. During the nine months following application for the CON, further questions were asked and five hearings were held. In April 1982, CHHC approved the program and the capital expenditures but did not approve the proposed 10% increase in drug revenue needed to support the services. The hospital ultimately committed funding for implementation of the program over three years. The net result of the application procedure was a delay in implementation of expanded pharmaceutical services.

Certificate of Need↗
PubMed1983

Physiologically based pharmacokinetic model for beta-lactam antibiotics I: Tissue distribution and elimination in rats.

The disposition characteristics of beta-lactam antibiotics in rats were investigated, and a physiologically based pharmacokinetic model capable of predicting the tissue distribution and elimination kinetics of these drugs was developed. Protein-binding parameters in rat serum were determined by equilibrium dialysis. Linear binding was found for penicillin G, methicillin, dicloxacillin, and ampicillin; however, nonlinear binding was observed for penicillin V and cefazolin. After intravenous bolus dosing, cefazolin was recovered almost completely in urine and bile, while for the penicillins, penicilloic acid was found to be the major metabolite. Biliary excretion of cefazolin followed Michaelis-Menten kinetics, and no significant inhibition of urinary secretion was observed after probenecid administration. The renal clearance of unbound drug was 0.82 ml/min with a reabsorption ratio (R) of 0.22. Tubular secretion was inhibited for the penicillins by probenecid plasma concentrations of 50 micrograms/ml, resulting in an R-value of 0.32. Erythrocyte uptake, serum protein binding, and tissue-to-plasma partition coefficient (Kp) were measured. Theoretical Kp values were calculated and found to be in good agreement with the Kp values for three of the antibiotics. Plasma and tissue concentrations (lung, heart, muscle, skin, gut, bone, liver, and kidney) were measured as a function of time at various doses for inulin and cefazolin in rats after an intravenous bolus dose, and were found to be in reasonable agreement with concentrations predicted by the model. These correlations demonstrate that the proposed model can accurately describe the plasma and tissue contributions of inulin and cefazolin in the rat and suggest that this model could have utility in predicting drug distribution in humans.

Animals↗
PubMed1983

Serum and tissue concentrations of cefoxitin and cefamandole in women undergoing hysterectomy.

To prevent infection in 40 patients who underwent vaginal or abdominal hysterectomy, each patient received a single 15-mg/kg dose of either cefoxitin or cefamandole by rapid (5-minute) intravenous injection before the operation. Samples of serum, myometrium, endometrium, ovaries, and tubes were obtained at various intervals after injection of the antibiotic and were assayed for cephalosporin concentration. Maximum tissue concentrations of 30 micrograms/g of both drugs were detected approximately 30 minutes after the dose, with levels dropping below 3 micrograms/g in approximately 2 hours. Although both antibiotics achieved closely similar concentrations in serum and tissues, the ratios of these levels to their usual mean minimum inhibitory concentrations for Bacteroides fragilis were appreciably higher for cefoxitin than for cefamandole. These pharmacokinetic observations support the current dosage recommendations for the use of cefoxitin in treating and preventing gynecologic infections, as well as the recommendation that it be administered shortly before the operation to maximize tissue levels during the perioperative period.

Adult↗
PubMed1982

In vivo inactivation of tobramycin by ticarcillin. A case report.

Inactivation of tobramycin sulfate by ticarcillin disodium was observed in a patient with impaired renal function. Tobramycin elimination half-life was seven hours with concurrent ticarcillin therapy but 35 hours without ticarcillin therapy. The magnitude of change cannot be attributed to changing renal function or tobramycin accumulation. The present case demonstrates that in vivo inactivation of tobramycin by ticarcillin can substantially increase the overall tobramycin elimination rate in patients with severe renal failure; however, in patients with normal renal function such inactivation is predicted to cause little change in overall tobramycin elimination rate.

Aged↗
PubMed1982

Pharmacokinetics of erythromycin in normal and alcoholic liver disease subjects.

The objective of this study was to compare the pharmacokinetic behavior of erythromycin in normal volunteers with that in subjects with alcoholic liver disease. Six normal volunteers received 500 mg erythromycin as an intravenous infusion or as two 250-mg enteric-coated tablets in a crossover fashion. The pharmacokinetics of erythromycin after intravenous administration was best described as a two-compartment model. The elimination half-life was 1.6 +/- 0.7 hours (mean +/- S.D.) after the intravenous dose and 2.0 +/- 0.7 hours after the oral dose. In patients with alcoholic liver disease the elimination half-life after oral administration of two 250-mg enteric-coated tablets was 3.2 +/- 0.5 hours, significantly different from that in normal subjects, probably due to impaired metabolism. The difference in half-life does not require dosage adjustment in this patient population. The systemic availability of erythromycin was 33.5 per cent (range 10.5 to 79.3 per cent).

Administration, Oral↗
PubMed1982

First and second generation cephalosporins.

Data on tissue levels of drugs are important, for they provide us with information on concentrations that can be achieved at the site of an infection. Yet many questions remain unanswered in this area such as whether it is better to achieve high levels in tissue rapidly as with bolus administration of a drug, or whether it is preferable to maintain levels of drug at lower but more prolonged levels, as with constant infusion administration of a drug. The goal in the future will be to correlate pharmacologic principles with the efficiency of various dosing programs and tissue levels in the clinical setting.

Bacteria↗
PubMed1982

Penetration of amoxicillin, cefaclor, erythromycin-sulfisoxazole, and trimethoprim-sulfamethoxazole into the middle ear fluid of patients with chronic serous otitis media.

Penetration into the middle ear of four antibiotics commonly used in treatment of otitis media was studied by administering a single oral dose of amoxicillin, cefaclor, erythromycin-sulfisoxazole, or trimethoprim-sulfamethoxazole to 83 children with chronic serous otitis media. The antibiotic was given 15-240 min before the removal of middle ear fluid (MEF) by ventilation tubes inserted through the tympanic membrane. At the time MEF was obtained, a sample of blood was drawn from the patient, and concentrations of antibiotic in both specimens were assayed either microbiologically by a disk diffusion method or by high-pressure liquid chromatography. Amoxicillin had the highest ratio of mean peak concentration in MEF to minimal inhibitory concentration (MIC) for the three most common pathogens of otitis media (Streptococcus pneumoniae, ampicillin-sensitive Haemophilus influenzae, and Streptococcus pyogenes), whereas trimethoprim-sulfamethoxazole had the highest ratio of mean peak concentration in MEF to MIC for ampicillin-resistant Haemophilus influenzae.

Amoxicillin↗
PubMed1982

Penetration of ceforanide and cefamandole into the right atrial appendage, pericardial fluid, sternum, and intercostal muscle of patients undergoing open heart surgery.

Doses of 30 mg of ceforanide or cefamandole per kg were administered intravenously to 26 patients just before their chests were opened for coronary artery bypass or cardiac valve replacement surgery. Samples of right atrial appendage, pericardial fluid, plasma, aortic wall, intercostal muscle, and sternum were obtained at different times after the antibiotic was injected, and these samples were assayed for cephalosporin concentration. For ceforanide the pre-bypass plasma half-life was 2.5 h, and the atrial appendage half-life was 2.1 h; for cefamandole the pre-bypass plasma half-life was 0.75 h and the atrial appendage half-life was 0.72 h. At 3 h the concentrations of ceforanide and cefamandole in atrial appendages were 28.0 and 5.0 micrograms/g, respectively. Ceforanide achieved higher and more sustained concentrations in other tissues than cefamandole. Considering the minimal inhibitory concentrations of these drugs for staphylococci, cefamandole and ceforanide should provide adequate protection against infection by these organisms for the duration of the surgical procedure.

Cardiac Surgical Procedures↗
PubMed1982

Applications of a minicomputer to clinical pharmacy services.

The application of a minicomputer system to clinical services and administrative record keeping is described. All applications were designed and implemented by pharmacists. Programs were created to increase the efficiency of collecting workload statistics for clinical services and to perform pharmacokinetic analyses of patient-specific data. The time required to generate quarterly workload reports decreased from 15-18 hours to 20-30 minutes. The use of the minicomputer also permitted a substantial expansion in the scope of the information collected and reported. The pharmacokinetic programs required approximately two minutes to calculate patient-specific peak and trough concentrations. The minicomputer system has increased the pharmacy department's administrative efficiency and encouraged staff pharmacist involvement in clinical services.

Computers↗
PubMed1981

A comparison of the penetration characteristics of cephapirin and cephalothin into right atrial appendage, muscle, fat, and pericardial fluid of pediatric patients undergoing open-heart operation.

Thirty-two pediatric patients having open-heart operation received a single dose of either cephalothin or cephapirin intravenously, 30 mg per kilogram of body weight, in the operating room, for prophylaxis before the chest cavity was opened. Samples of right atrial appendage, pericardial fluid, muscle, fat, and plasma were obtained at various time intervals after injection of the antibiotics, and assayed for cephalosporin concentration. The concentration-time profiles of cephalothin and cephapirin in atrial appendage, muscle, fat, and plasma were identical. Cephapirin produced higher total and free concentrations in pericardial fluid compared with cephalothin. This presumably was due to the lower protein binding of cephapirin. Antibiotic concentrations above the minimal inhibitory concentration for Staphylococcus aureus and S. epidermidis were present in myocardial tissue for at least 90 minutes after the dose was administered. These data support the need to administer these antibiotics shortly before surgical intervention and, if the operation is prolonged, the need to administer a second dose of antibiotic.

Adipose Tissue↗
PubMed1981

Disopyramide hemodialysis and kinetics in patients requiring long-term hemodialysis.

Disopyramide hemodialysis and kinetics after 200 mg orally in six patients receiving long-term hemodialysis were examined. Mean volume of distribution (area) was 66.5 +/- 13 l. Mean times of the peak serum concentration and mean peak serum concentration were 2.3 +/- 0.9 hr and 3.1 +/- 0.9 microgram/ml. Mean absorption half-life (t 1/2) was 21.6 +/- 12.5 min. Mean disopyramide elimination t 1/2 during dialysis was 16.8 +/- 11.9 hr, not significantly different from mean elimination t 1/2 without dialysis of 16.1 +/- 5.2 hr. End-dialysis bath concentrations of disopyramide showed that not more than 2.4% of the dose was dialyzed during a 2-hr dialysis period. Our data indicate that at therapeutic concentrations disopyramide was not appreciably dialyzed.

Adult↗