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Biomedical subjects

S F Kowalsky

Publications and source records attributed to S F Kowalsky.

At least 19 recordsLinked to original sources
PubMed1996

Ciprofloxacin pharmacokinetics in burn patients.

Many drugs exhibit altered pharmacokinetic parameters in burn patients. We prospectively evaluated the pharmacokinetics of ciprofloxacin in eight burn patients with active infections. Each patient received a 400-mg dose of ciprofloxacin intravenously (i.v.) every 8 h, with each dose infused over 1 h by using a rate control device. Blood samples for analysis of plasma ciprofloxacin concentrations, determined by high-performance liquid chromatography, were obtained immediately predose, at the end of the infusion, and 1, 2, 3, 4, 5, 6, and 7 h after the end of the infusion. Urine was collected from 0 to 2, 2 to 4, and 4 to 8 h following the same dose, and an aliquot was saved for determination of the ciprofloxacin concentration. Urine was also collected for 24 h prior to this dose for measurement of creatinine clearance (CLCR). Pharmacokinetic parameters were estimated by noncompartmental analysis. Mean maximum and minimum plasma ciprofloxacin concentrations were 4.2 +/- 1.1 and 0.70 +/- 0.55 microgram/ml, respectively. Mean values for clearance (CL), renal clearance (CLR), volume of distribution, terminal elimination rate constant, half-life (t1/2), and area under the concentration-time curve (AUC) were 29.1 +/- 17.5 liters/h, 13.5 +/- 10.1 liters/h, 1.75 +/- 0.41 liters/kg, 0.222 +/- 0.098 h-1, 4.5 +/- 3.9 h, and 20.7 +/- 16.6 micrograms.h/ml, respectively. CL was higher and t1/2 was shorter than noted in previous studies of acutely ill, hospitalized patients. A good correlation was noted between creatinine clearance CL(CR) and both total ciprofloxacin CL (r = 0.85) and CLR (r = 0.84). A moderate inverse correlation was noted between percent body surface area burned and total ciprofloxacin CL (r = -0.55). An AUC/MIC ratio above 125 SIT-1 (where SIT is serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in five of eight patients (63%) with a MIC of 0.25 microgram/ml. At a ciprofloxacin dosage of 400 mg i.v. every 12 h, an AUC/MIC ratio above 125 SIT-1 would have been achieved in only two of eight patients (25%). We conclude that ciprofloxacin CL is highly variable, but generally increased, in burn patients compared with that in acutely ill, general medical and surgical patients. Because of an increase in CL, a ciprofloxacin dosage of 400 mg i.v. every 8 h is more likely to produce the desired response in burn patients than the same dose given every 12 h.

Adolescent↗
PubMed1995

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected].

BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

Acute Disease↗
PubMed1995

Enteric absorption of ciprofloxacin during the immediate postoperative period.

We studied the enteric absorption of ciprofloxacin immediately following major abdominal surgery to determine if this drug could replace parenteral agents. Nine critically ill subjects received ciprofloxacin, 750 mg, every 12 h for 48 h via nasogastric tube. Drug concentrations were measured after the first and fourth doses. There was insignificant absorption after the initial dose, Cmax = 0.6 +/- 0.6 (mg/L) and AUC0-12 = 3.5 +/- 3.2 (mg.h/L). Unfortunately, serum ciprofloxacin concentrations were also minimally detectable in three of nine subjects after the fourth dose. Enteric absorption of ciprofloxacin, therefore, was erratic and unpredictable in critically ill patients following major abdominal surgery.

Abdomen↗
PubMed1993

Pharmacokinetics of ciprofloxacin in subjects with varying degrees of renal function and undergoing hemodialysis or CAPD.

The pharmacokinetics of a single, oral dose of 750 mg of ciprofloxacin were studied in 35 subjects with various degrees of renal function (Group 1, Clcr > or = 80 ml/min; Group II, Clcr 50-79 ml/min; Group III, Clcr 10-49 ml/min) and on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Blood, urine and CAPD dialysate samples were collected over a period of 48 hours after dosing. Data were fitted using non-linear, least squares regression. The mean Cmax was 3.4 +/- 1.0 mg/l and tmax was 2.3 +/- 0.9 hours. The mean AUC in Group I was 14.7 mg.h/l, Group II was 33.7 (p < 0.001), Group III 63.8 (p < 0.001), HD 57.9 (p < 0.0001) and CAPD 44.3 (p < 0.001). Half-life in Group I was 4.6 h, and was shorter than Group III (11.1 h, p < 0.001), HD (13.4 h, p < 0.001) and CAPD (8.9 h, p < 0.001). Total body clearance and renal clearance demonstrated significant differences also. The dialysis clearance in CAPD patients was 0.53 +/- 0.39 l/h. Peritoneal effluent concentrations varied from 0.6 mg/l during the first exchange, to a peak of 2.2 mg/l during the second, to 0.13 mg/l in the 48 hour (9th) exchange. Dosage adjustments of ciprofloxacin in the presence of renal insufficiency are indicated for subjects with a Clcr < 20 ml/min/1.73m2.

Administration, Oral↗
PubMed1992

Trimetrexate for Pneumocystis carinii pneumonia in patients with AIDS.

OBJECTIVE: The primary objective of this article is to introduce readers to the use of a new agent, trimetrexate (TMTX), in the treatment of Pneumocystis carinii pneumonia (PCP). The article also gives the readers an overview of PCP and discusses some of the controversies surrounding it. Pharmacokinetic data and clinical trials are reviewed, as well as adverse effects, drug interactions, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: As both pharmacokinetic and clinical trials were few in number, all available trials were reviewed. DATA EXTRACTION: Pharmacokinetic data from trials involving patients with AIDS was sparse; therefore, those involving oncology patients, including a pediatric population, were included. Although more trials need to be done in AIDS patients, the results from the oncologic trials give us a baseline from which to extrapolate. All clinical trials available at the time of publication were reviewed as were all of the preliminary results from three ongoing trials, which were made available through a personal communication. DATA SYNTHESIS: TMTX has been found to be 1500 times more potent than trimethoprim as a dihydrofolate reductase inhibitor, and has the potential to provide an effective therapeutic option for PCP. TMTX is a lipid-soluble analog of methotrexate and is thus capable of greater penetration into Pneumocystis cells, which lack the folate membrane transport system necessary to take up classic folate structures like leucovorin and methotrexate, thereby negating any clinical effectiveness of methotrexate and allowing leucovorin to be used for host cell rescue. TMTX's pharmacokinetic parameters best fit a multicompartmental model with a terminal half-life of up to 12 hours. It is cleared both hepatically and renally with up to 41 percent excreted unchanged in the urine. Although TMTX's pharmacokinetic parameters are variable, the need for plasma concentration monitoring at present is unclear, as no dose-response relationship has been established.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Fluconazole: a new antifungal agent.

The chemistry, activity, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and administration of fluconazole are reviewed. Fluconazole is a triazole antifungal agent labeled for use in the treatment of oropharyngeal and esophageal candidiasis and cryptococcal meningitis. Like the imidazoles, fluconazole inhibits the C-14 demethylation of lanosterol, but it has little or no effect on mammalian cytochrome P-450 enzymes. Fluconazole's activity in vitro does not reflect its effectiveness in vivo. Pharmacokinetic characteristics include water solubility and excellent bioavailability, low protein binding, extensive tissue distribution, and penetration into the cerebrospinal fluid. Fluconazole is eliminated primarily by the kidneys; dosage adjustments are necessary in patients with renal insufficiency. Studies have shown fluconazole to be effective in patients with cryptococcal meningitis and candidiasis, but the superiority of fluconazole over such agents as amphotericin B, ketoconazole, clotrimazole, and itraconazole remains to be proved. Fluconazole has shown varying degrees of success in the treatment of other systemic mycoses. The adverse effects of fluconazole are relatively infrequent and are primarily gastrointestinal. Tolbutamide, warfarin, rifampin, cyclosporine, and phenytoin interact with fluconazole. The drug is available in both oral and intravenous formulations. Fluconazole is a broad-spectrum antifungal drug that appears to be similar in efficacy to other antifungals in the treatment of some systemic mycoses. More studies must be completed before fluconazole can be recommended as a first-line antifungal therapy.

Animals↗
PubMed1991

Disposal of CAPD waste in the community.

Fifty-nine patients returned a confidential mailed questionnaire, to determine their procedures for disposal of CAPD waste including bags, fluids and needles, and to assess their instruction and opinions on health risks from their wastes. Patients came predominantly from rural communities. Sixty four percent used disposal boxes for used needles, 80% discarded drained bags in the garbage without wrapping them in plastic and 7 to 17% of patients discarded needles straight to the garbage, depending on circumstances. Thirty seven percent did not recall receiving instruction on waste disposal, and of those who did, instructions came predominantly from nurses. Twenty of 32 patients who had suffered peritonitis disposed of their bags during peritonitis in the same manner as when they did not have peritonitis. Most patients (61%) felt issues dealing with CAPD waste disposal were "important" or "very important", but fewer "agreed" or "strongly agreed" that it posed a health risk to others (16%) or to the environment (10%). Inconsistencies in methods of disposal and potential risks of infection dictate that guidelines must be developed to deal with these issues.

Adult↗
PubMed1990

Comparative serum bactericidal activity of ceftizoxime/metronidazole, ceftizoxime, clindamycin, and imipenem against obligate anaerobic bacteria.

We compared the bactericidal activity of serum obtained from healthy volunteers after single intravenous infusions of the combination of ceftizoxime (1 g) plus metronidazole (1 g) and after infusions of ceftizoxime (2 g), clindamycin (900 mg), and imipenem (1 g) against six obligate anaerobes. All agents were bactericidal but only the combination regimen resulted in bactericidal titres greater than 1:2 at 12 h for all the Bacteroides fragilis group organisms. High titres against Fusobacterium necrophorum and anaerobic Gram-positive cocci were attained with ceftizoxime/metronidazole, ceftizoxime, and imipenem 12 h after the dose. Imipenem and the combination of ceftizoxime/metronidazole had the greatest area under the bactericidal curve (AUBC) against the Bacteroides species. Clindamycin had a significantly smaller AUBC than other regimens for all strains tested except B. thetaiotaomicron. Clinical trials are needed to assess the efficacy and cost-benefit ratio of a 12 h dosing regimen of ceftizoxime in combination with metronidazole for treating mixed aerobic/anaerobic infections.

Adult↗
PubMed1990

Lindane (Kwell)-induced aplastic anemia.

Numerous toxic exposures have been implicated in causing aplastic anemia. Thirteen cases of aplastic anemia and 5 cases of other blood dyscrasias, eg, red blood cell aplasia and thrombocytopenia, associated with lindane, have been reported in the literature. However, aplastic anemia secondary to the scabicidal product (lindane [Kwell]) has not been documented, to our knowledge. We present the case of a 21-year-old man with a diagnosis of aplastic anemia, known prolonged exposure to lindane, and documented elevated serum lindane levels. His clinical course is described as well as various defects are explored for the aplasia.

Administration, Topical↗
PubMed1989

Streamlining antimicrobial therapy through pharmacists' review of order sheets.

The impact of a pharmacy-conducted intervention program designed to contain costs by "streamlining" antimicrobial therapy is described. Streamlining of antimicrobial therapy may involve simplifying routes of administration, decreasing the dose or frequency of antimicrobial administration, or converting from multiple-agent therapy to single-agent therapy. Beginning on December 1, 1987, pharmacists at this university-affiliated teaching hospital used the antimicrobial order sheet (AOS) filled out by all prescribers of anti-infective agents to identify orders that were potential candidates for streamlining. Interventions involved a discussion between the pharmacist and prescriber in which the pharmacist specified the reasoning behind the recommended change. For each recommendation that was accepted by the prescriber, the cost savings per day was determined by subtracting the daily cost of the recommended streamlined therapy from the daily cost of the original "problem" therapy. Data collection continued until May 1, 1988. During that five-month period, 162 out of 173 pharmacist-initiated streamlining recommendations were accepted by prescribers, resulting in a total cost savings of $19,864. The average cost savings per intervention was $122.62. The most frequent intervention involved decreasing the frequency of i.v. administration, decreasing the dose, or both. The intervention that resulted in the greatest average cost savings involved simplifying the route of administration or discontinuing antimicrobial therapy entirely. The projected annual cost savings of this program is $47,700. By using information from AOSs to identify problem antimicrobial orders, pharmacists were able to recommend streamlining of antimicrobial therapies that resulted in an average cost savings of about $122 per intervention.

Anti-Infective Agents↗
PubMed1986

Effect of the acetylator phenotype on amrinone pharmacokinetics.

Ten healthy male subjects were phenotyped with isoniazid for their acetylator status and then received intravenous amrinone at a dose of 75 mg during a period of 10 minutes. Blood samples were drawn at specified times during a 24-hour period after dosing. Plasma concentrations of amrinone were determined by a specific HPLC method. The plasma concentration data were fitted to a biexponential model by nonlinear regression. The mean apparent first-order elimination t1/2 for amrinone in the slow acetylators was 4.4 hours, whereas it was 2.0 hours in the fast acetylators (P less than 0.05). There was little difference in the volume of distribution at steady state. Clearance was lower in the slow acetylators, 16.6 L/hr, than in the fast acetylators, 37.2 L/hr (P less than 0.05). The AUC was higher for the slow acetylators, 4.96 micrograms X hr X ml-1, than for the fast acetylators, 2.20 micrograms X hr X ml-1 (P less than 0.01). Concentrations of amrinone and its N-acetyl metabolite in the urine from each volunteer were determined. The ratio of N-acetylamrinone to amrinone was calculated and, as expected, the fast acetylators had a higher ratio than did the slow acetylators (P less than 0.01).

Acetylation↗
PubMed1986

Clindamycin phosphate kinetics in subjects undergoing CAPD.

The kinetics of intraperitoneally administered clindamycin phosphate were studied in 9 volunteer subjects undergoing CAPD. Volunteers were assigned to 2 groups with the first group receiving clindamycin phosphate 300 mg/l in exchanges 1 through 5, and the second group receiving clindamycin phosphate 300 mg/l in exchange 1, and then 30 mg/l in exchanges 2 through 5. Clindamycin serum and dialysate effluent levels were determined by bioassay. When admixed with dialysate fluid and instilled into the peritoneal cavity, clindamycin phosphate is rapidly activated. Serum concentrations of clindamycin were rapidly achieved in both groups during the first exchange. Subjects in groups I and II had peak serum levels of active drug within 3 (3.94 ug/ml) and 5 (7.35 ug/ml) h, respectively. These results support the practice of not only administering intraperitoneal clindamycin phosphate to treat CAPD-related peritonitis, but using this route of administration to treat systemic infections due to susceptible bacteria in patients without intravenous access.

Adult↗