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Biomedical subjects

M A Gill

Publications and source records attributed to M A Gill.

At least 55 records · Page 3Linked to original sources
PubMed1992

Determination of fluconazole in human serum by solid-phase extraction and reversed-phase high-performance liquid chromatography.

A simple, rapid, and accurate reversed-phase octadecylsilyl high-performance liquid chromatographic method using solid-phase column extraction is described for measuring fluconazole in human serum. The column eluent was monitored by ultraviolet absorption at 210 nm. Fluconazole was extracted from diluted serum by adsorption on a small Bond-Elut C18 cartridge after the addition of UK48,134 as the internal standard and recovered by elution with methanol. The methanol was then evaporated to dryness and the residue reconstituted in 200 microliters of mobile phase and filtered prior to injecting an aliquot (50 microliters) onto an Adsorbosphere C18 column (4.6 x 250 mm, 5 microns particle size), using a mobile phase of 25 mM tris(hydroxymethyl)aminomethane-phosphate buffer (pH 7.0):acetonitrile (75:25, vol/vol). The retention times were 6.6 min for fluconazole and 9.0 min for the internal standard. The assay was precise, with inter- and intraassay coefficients of variation of less than or equal to 2.9% and less than or equal to 2.1%, respectively, and with good linearity (r = 1.000) in the range of 0.1 to 25 micrograms/ml. The duration of each analysis was 15 min and the minimum detectable serum concentration was 0.1 microgram/ml.

Administration, Oral↗
PubMed1992

Stability of ranitidine hydrochloride with aztreonam, ceftazidime, or piperacillin sodium during simulated Y-site administration.

The stability of ranitidine hydrochloride after being mixed with commonly used i.v. beta-lactam antibiotics and administered by simulated Y-site injection was studied. Solutions of ranitidine 1 mg/mL (as the hydrochloride salt), aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), and piperacillin 30 mg/mL (as the sodium salt) were prepared by reconstitution in i.v. mini-bags. To simulate Y-site injection, 2 mL of ranitidine hydrochloride was mixed with 2 mL of each antibiotic in glass test tubes. These admixtures were prepared in triplicate and stored at room temperature under fluorescent light. Concentrations of each drug in each admixture were determined by stability-indicating high-performance liquid chromatography immediately and after one, two, and four hours. Aztreonam, ceftazidime, and piperacillin each retained more than 95% of the original concentration for at least four hours when mixed 1:1 with ranitidine. Ranitidine retained more than 90% of its original concentration for at least four hours when combined with each of the other drugs. Ranitidine 1 mg/mL (as the hydrochloride salt) and aztreonam 16.7 mg/mL, ceftazidime 20 mg/mL (with sodium carbonate), or piperacillin 30 mg/mL (as the sodium salt) were stable for at least four hours during simulated Y-site administration.

Anti-Bacterial Agents↗
PubMed1991

Utility of a transdermal delivery system for antihypertensive therapy. Part 1.

A retrospective evaluation of patient-level Medicaid claims data from two states was undertaken to discern the fiscal utility of transdermally delivered clonidine versus both the oral formulation of clonidine and oral formulations of eight other antihypertensive agents. In the first phase of our two-part study, we compared paid claims data (n = 1,135) from Florida for transdermal and oral clonidine. Multivariate regression analysis was used to evaluate the incremental impact of six variables on health-care expenditures in the first year after patients were given a diagnosis of hypertension. These variables were: age, gender, prior utilization of medical services, regimen complexity, and dosage formulation. Patients prescribed transdermal clonidine experienced a significant (p less than or equal to 0.001) increase in prescription expenditures and significant reductions in the use of physician (p less than or equal to 0.05), laboratory (p less than or equal to 0.10), and hospital (p less than or equal to 0.05) services. Moreover, savings were maximized (p less than or equal to 0.001) where multi-drug regimens incorporated the transdermal delivery system. In the second phase of our study we compared paid claims data (n = 8,894) from South Carolina for transdermal clonidine and for nine oral antihypertensive agents: atenolol, captopril, clonidine, diltiazem, enalapril, metoprolol, prazosin, terazosin, and verapamil-SR. Once again, regression analysis was used, this time to evaluate the incremental impact of five variables on health-care expenditures in the first year post diagnosis: age, gender, prior utilization of medical services, regimen complexity, and Medication Possession Ratio (MPR), an index of compliance. The data from part 2 of our study revealed that patients assigned a b.i.d. oral antihypertensive agent experienced a significant reduction (p less than or equal to 0.05) in MPR and a significant (p less than 0.05) increase in health-care expenditures when compared to patients prescribed the transdermal delivery system and to patients prescribed once-daily oral medications. These data confirm previous findings concerning the impact of complicated dosing regimens on compliance in hypertensive patients. In this two-part paper we report the data from both phases of our study.

Administration, Cutaneous↗
PubMed1991

Pharmacokinetics of peptide T in patients with acquired immunodeficiency syndrome (AIDS).

1. The pharmacokinetics of Dala1-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiency disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intravenous (i.v.) or intranasal (i.n.), via metered sprayer, administration. 2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearance rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA. 3. Bioavailability, determined for a 2 mg test dose in six individuals was 9.3 +/- 6.9 nmol/L. Peak plasma levels of 41 +/- 30 nmol/L after 10 mg i.n., 2.8 +/- 5.9 nmol/L after 2 mg i.n., and 0.13 +/- 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Intramuscular imipenem as adjuvant therapy for acute cholecystitis and perforated or gangrenous appendicitis.

An open-label prospective study was performed employing intramuscularly administered imipenem as an adjunct to surgery in 20 patients with acute cholecystitis and 24 patients with perforated or gangrenous appendicitis. Three (12.5%) septic failures occurred in appendicitis patients and 2 (10%) failures in cholecystitis patients. There were no deaths. Adverse effects were minor, and there was no toxicity. Although failures were not associated with in vitro resistance, Pseudomonas spp. were recovered from 2 of 3 appendicitis failures. Intramuscular imipenem appeared to be an effective single-drug antimicrobial when used as an adjunct to surgery in patients with acute cholecystitis or perforated appendicitis. It should be a more cost-effective alternative to the current multiple-drug therapy frequently employed in patients with intra-abdominal sepsis.

Adult↗
PubMed1991

Analysis of cefepime tissue penetration into human appendix.

Cefepime is a new extended-spectrum cephalosporin with gram-positive and gram-negative coverage including Staphylococcus aureus and Pseudomonas aeruginosa. We evaluated the drug's plasma, peritoneal fluid, and appendix tissue concentrations in patients with a postoperative diagnosis of perforated or gangrenous appendicitis. Patients 18 years of age or older were randomly assigned to receive either cefepime 2 g every 12 hours plus metronidazole 500 mg every 6 hours intravenously, or gentamicin 1.5 mg/kg plus clindamycin 900 mg every 8 hours intravenously. During surgery, appendix tissue, plasma, and peritoneal fluid samples were obtained, and frozen at -70 degrees C for high-pressure liquid chromatographic analysis. Thirty-five patients with perforated (26) or gangrenous (9) appendicitis had concentrations acceptable for analysis. The mean time between the administration of cefepime and the time of sampling (referred to as delta time) was 5.99 +/- 3.75 hours (mean +/- SD). The values for plasma (n = 34), tissue (n = 33), and peritoneal fluid (n = 25) concentrations were 16.27 +/- 21.87 micrograms/ml, 4.84 +/- 6.15 micrograms/g, and 14.4 +/- 22.84 micrograms/ml, respectively. The appendix tissue:plasma ratio was 0.66 +/- 0.52 and the peritoneal fluid:plasma ratio was 0.66 +/- 0.51. Spearman rank correlations indicated statistically significant correlations between plasma concentration (r = -0.889; p less than 0.0001), peritoneal fluid concentration (r = -0.783; p = 0.0002), and appendix tissue concentration (r = -0.704; p = 0.0016) versus delta time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Intraoperative concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue.

To evaluate concentrations of ofloxacin in serum, bile fluid, and gallbladder wall tissue after intravenous administration, patients greater than or equal to 16 years old diagnosed with acute cholecystitis were randomly assigned to receive ofloxacin (400 mg) intravenously every 12 h or ceftazidime (2 g) intravenously every 8 h. Doses of each regimen were given preoperatively. Serum, bile fluid, and gallbladder wall tissue samples of consecutive patients in the ofloxacin group were obtained intraoperatively. The samples were frozen at -70 degrees C until analyzed by high-pressure liquid chromatography. Twenty-three patients (6 males and 17 females) were evaluated. The mean (+/- the standard deviation) ofloxacin concentrations in serum, bile fluid, and gallbladder wall tissue were 2.9 +/- 2.4 and 6.0 +/- 7.9 micrograms/ml and 3.1 +/- 2.9 micrograms/g, respectively. The mean number of doses each patient received before surgery was 5.3 +/- 3.0, and the mean delta time (time elapsed between last antibiotic administration and when intraoperative samples were obtained) was 9.6 +/- 7.5 h. The mean tissue-to-serum ratio was 1.2 +/- 0.5, and the mean bile-to-serum ratio was 2.3 +/- 1.4. The mean serum ofloxacin concentrations were not statistically different from the concentrations in bile (P = 0.1) and tissue (P = 0.7) at the mean delta time. The study revealed that concentrations of ofloxacin in serum, bile fluid, and gallbladder tissue after intravenous dosing were adequate against susceptible organisms found in the biliary tract.

Adult↗
PubMed1990

Treatment of intra-abdominal infections: cost comparison of ampicillin/sulbactam and clindamycin/gentamicin.

The cost of 2 g ampicillin/1 g sulbactam given IV piggyback qid was compared with 900 mg clindamycin admixed with 1.5 mg/kg gentamicin given IV piggyback tid for the treatment of perforated or gangrenous appendicitis in 116 patients. Fifty-eight ampicillin/sulbactam-receiving patients incurred greater costs for IV supplies (+104.6/patient vs +67.9/patient) and nursing administration costs (+16.5/patient vs +10.7/patient). On the other hand, pharmacist and technician preparation costs were greater for the 58 clindamycin/gentamicin-receiving patients (+15.4/patient vs +13.3/patient). The clindamycin/gentamicin-receiving patients also incurred additional changes for laboratory fees and pharmacokinetic monitoring--+18.7/patient and +36.1/patient, respectively. When incorporating all cost parameters, there were no statistically significant differences in mean total drug therapy costs between the two treatment regimens--+433.3 +/- +58.5/patient for ampicillin/sulbactam and +373.8 +/- +86.2/patient for clindamycin/gentamicin.

Ampicillin↗
PubMed1990

Controlled comparison of cefmetazole with cefoxitin for prophylaxis in elective cholecystectomy.

Prophylactic antibiotics are given routinely to patients undergoing surgical treatment of the biliary tract to prevent postoperative infection if risk factors for postoperative sepsis are present. Cefmetazole (CM) is a new broad spectrum parenteral cephamycin antibiotic. This drug possesses a spectrum of activity against a wide range of gram-negative and gram-positive bacteria that is similar to cefoxitin (CX), an antibiotic widely used for prophylaxis with operations upon the abdomen. In this study, there was a random selection of two patients to receive CM to every one patient to receive CX. The dose of CM was 1 gram given intravenously every eight hours for three doses beginning 30 minutes before the operation; three doses of CX were given intravenously, 2 grams every six hours. Fifty-two evaluable patients comprised the CM group and 26, the CX group. The risk factors for postoperative infection were acute cholecystitis (CM, seven patients; CX, one patient), evidence from imaging procedure suggesting need for exploration of the common duct (CM, six; CX, one), hyperbilirubinemia (CM, eight; CX, four), hyperamylasemia (CM, 17; CX, seven); age of 60 years or more (CM, six; CX, one), obesity (CM, 36; CX, 14) and diabetes mellitus (CM, four; CX, five). Operative bactibilia and the organisms were comparable in both groups. Postoperative days of fever greater than or equal to 38 degrees C. (oral) (CM, 0.83 +/- 1.20; CX, 0.58 +/- 0.96) and hospitalization (CM, 6.59 +/- 2.20; CX, 5.04 +/- 1.26) were similar. Postoperative septic complications at the operative site occurred in two patients in the CM group (4 per cent) and in none of the patients in the CX group (p = 0.4; N.S., Fischer exact test). These two antibiotics had similar efficiency in preventing postoperative infections.

Adult↗
PubMed1989

Cost analysis of two clindamycin dosing regimens.

A clinical trial of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg (eight-hourly group) versus clindamycin 600 mg q6h with gentamicin 1.5 mg/kg given separately (six-hourly group) was analyzed for relative cost containment. Acquisition costs were significantly higher for the six-hourly group for intravenous supplies ($181.5 +/- 47.8) when compared with the eight-hourly group ($67.6 +/- 21.6) (p less than 0.05). Nursing administration costs were greater for the six-hourly group ($28.6 +/- 7.5) compared with ($10.7 +/- 3.4) for the eight-hourly group (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for pharmacist and technician manufacturing cost for the six-hourly group ($15.4 +/- 4.0) compared with the eight-hourly group ($13.3 +/- 4.3). Incorporating all appropriate costs, the mean total drug therapy costs were significantly greater (p less than 0.05) for clindamycin 600 mg q6h ($527.4 +/- 143.0) compared with clindamycin 900 mg q8h ($433.3 +/- 99.2). The dosing of clindamycin 900 mg q8h admixed with gentamicin 1.5 mg/kg is a more cost-effective method of drug delivery with similar efficacy and safety when compared with clindamycin 600 mg q6h with gentamicin given separately.

California↗
PubMed1989

A cost comparison of intramuscular versus intravenous imipenem.

Previously reported clinical trials of imipenem-cilastatin 500 mg given intravenously every 6 hours (intravenous group) and imipenem-cilastatin 750 mg given intramuscularly every 12 hours (intramuscular group) were analyzed for relative cost savings. Acquisition costs were significantly higher for the intravenous group for intravenous supplies (30.6 +/- 7.9 dollars) when compared to the intramuscular group (0.98 +/- 0.03 dollars) (p less than 0.05). Also, significantly higher cost (p less than 0.05) was noted for salaries of pharmacists and technicians for manufacturing in the intravenous group (5.8 +/- 1.5 dollars) as compared to the intramuscular group (2.4 +/- 0.7 dollars). Nursing administration costs were greater for the intramuscular group (15.6 +/- 4.8 dollars) when compared to the intravenous group (11.7 +/- 3.0 dollars). Incorporating all appropriate costs, the mean total drug therapy costs (TRX$) were significantly greater (p less than 0.01) for the intravenous group (458.17 +/- 175.17 dollars) as compared to the intramuscular group (298.0 +/- 114.76 dollars). Thus, the dosing of imipenem-cilastatin 750 mg intramuscularly every 12 hours is a more cost effective method of drug delivery with equal efficacy and safety when compared to imipenem-cilastatin 500 mg given intravenously every 6 hours.

Adolescent↗
PubMed1989

Evaluation of two different dosage regimens of clindamycin and the penetration into human appendix.

The study objective was to evaluate serum, peritoneal fluid, and appendix tissue concentrations of clindamycin using two differing clindamycin regimens. Patients age 16 years and older who were about to undergo appendectomies were randomly assigned to receive gentamicin 1.5 mg/kg every 8 h admixed with clindamycin 900 mg every 8 h (8-h group) or clindamycin 600 mg every 6 h given separately (6-h group). Doses of each regimen were given preoperatively. Serum, peritoneal fluid, and appendix tissue samples were obtained intraoperatively, and frozen at -70 degrees C for gas chromatographic drug analysis. Twenty-one patients were evaluated, 11 patients in the 8-h group and 10 patients in the 6-h group. Values are reported as means +/- standard deviations. The values in the 8-h group were 12.3 +/- 14.1 micrograms/ml, 8.7 +/- 3.9 micrograms/ml, and 9.8 +/- 10.3 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The values in the 6-h group were 9.7 +/- 5.1 micrograms/ml, 5.8 +/- 5.3 micrograms/ml, and 6.2 +/- 4.9 micrograms/g for serum, peritoneal fluid, and appendix tissue, respectively. The 6-h group received more doses preoperatively (1.8 +/- 0.6) than the 8-h group (1.2 +/- 0.4; p less than 0.05). No differences in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue for the 8-h group and the 6-h group were noted. The study revealed a similarity in penetration of clindamycin into the serum, peritoneal fluid, and appendix tissue using either clindamycin 900 mg given by intermittent intravenous infusion every 8 h admixed with gentamicin or clindamycin 600 mg given every 6-h separately.

Adolescent↗
PubMed1988

Sulbactam: a beta-lactamase inhibitor.

The chemistry, pharmacology, microbiology, pharmacokinetics, clinical efficacy, and adverse effects of sulbactam are reviewed. Sulbactam is a competitive, irreversible beta-lactamase inhibitor. Its binding to penicillin-binding proteins imparts weak intrinsic antibacterial activity. Synergy of sulbactam with beta-lactam antibiotics is most marked in bacterial species in which beta lactamase is a major mechanism of resistance. Sulbactam sodium is available in combination with ampicillin sodium for injection in a 1:2 ratio of sulbactam to ampicillin. Sultamicillin, an oral prodrug that is hydrolyzed to equimolar amounts of ampicillin and sulbactam, is in clinical trials. Ampicillin and sulbactam have similar pharmacokinetic properties. Sulbactam-ampicillin appears to be most useful for the treatment of polymicrobial aerobic or anaerobic infections and uncomplicated gonorrhea. Persistence, relapse, and superinfections have been reported after sulbactam-ampicillin treatment of urinary-tract and respiratory-tract infections. The combination is not effective against pseudomonal infections. Sulbactam-ampicillin is generally well tolerated. By restoring or expanding the activity of older, well-established beta-lactam antibiotics, sulbactam offers a new approach to the management of bacterial infections; the minimal toxicity of sulbactam-ampicillin makes the combination appealing for the treatment of gram-negative nonpseudomonal and anaerobic infections.

Chemical Phenomena↗
PubMed1987

Surgically treated gangrenous or perforated appendicitis. A comparison of aztreonam and clindamycin versus gentamicin and clindamycin.

A randomized, double-blinded, controlled clinical study of 84 patients with surgically treated gangrenous or perforated appendicitis was done to compare the efficacy of the combination of aztreonam, the first monobactam antibiotic, with gentamicin when either was combined with clindamycin. Fifty-six patients who were treated with aztreonam and clindamycin (A/C) and 28 patients who were treated with gentamicin and clindamycin (G/C) fulfilled criteria for evaluation. A matched historic control group of 56 G/C patients was also included for comparison. All measures of outcome, including days of fever, hospitalization, antibiotic therapy, and the incidence of antibiotic failures, were similar. It was concluded that aztreonam was as effective as gentamicin in this study and may offer some advantages with regard to toxicity and serum drug level monitoring.

Adult↗