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Biomedical subjects

J M Spivey

Publications and source records attributed to J M Spivey.

7 recordsLinked to original sources
PubMed1992

Dose-ranging pharmacokinetic study of ciprofloxacin after 200-, 300-, and 400-mg intravenous doses.

OBJECTIVE: To assess the pharmacokinetics and tolerance of ciprofloxacin after the administration of single intravenous doses of 200, 300, and 400 mg. DESIGN: Double-blind, three-period, randomized, crossover trial. SETTING: Private, university-affiliated, hospital-based, clinical research center. PATIENTS: Normal healthy male volunteers, 18-40 years of age. INTERVENTIONS: Subjects received 200-, 300-, and 400-mg single intravenous doses of ciprofloxacin via 30-minute infusions in random sequence. MAIN OUTCOME MEASURES: Serum ciprofloxacin concentrations were determined by HPLC after each dose and the results were used to derive pharmacokinetic parameters. Tolerance was assessed by reported and observed adverse events, urine microscopic examinations for crystals, and examination of intravenous infusion sites. RESULTS: The mean area under the time curve (AUC) values displayed linearity with respect to the administered dose. No statistical differences were observed in total body clearance, steady-state volume of distribution, or elimination half-life with respect to dose administered. The mean total body clearance, steady-state volume of distribution, or elimination half-life ranged from 36 to 41 L/h, 146 to 169 L, and 3.5 to 3.7 h for the 200-, 300-, and 400-mg doses, respectively. Adverse effects, including venous irritation (four subjects) and crystalluria (two subjects), were mild and did not require withdrawal of any subject from the study. CONCLUSIONS: Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed.

Adolescent↗
PubMed1992

The postantibiotic effect.

The factors that affect the presence and duration of the post-antibiotic effect (PAE) for different antimicrobial agents are described, and the clinical importance of the PAE is discussed. Proposed mechanisms by which the PAE occurs include both nonlethal damage induced by the antimicrobial agent and a limited persistence of the antimicrobial agent at the bacterial binding site. The specific microorganism-antimicrobial combination is the most important factor to influence the presence and duration of the PAE. Additional factors are antimicrobial combinations and experimental conditions, including the antimicrobial concentration and the length of the antimicrobial exposure. Most antimicrobial agents produce a PAE when tested against gram-positive cocci. However, against gram-negative bacilli, beta-lactam antibiotics (except for imipenem) have a minimal, or even a negative, PAE. Aminoglycosides, inhibitors of protein and nucleic acid synthesis, and fluoroquinolones have PAEs against gram-negative bacteria that range from one to four hours. In vivo PAEs are generally longer than in vitro PAEs for the same microorganism-antimicrobial combination. In human studies, aminoglycosides, which have an extended PAE against gram-negative bacilli, have been effective when given in once-daily dosing regimens that allow serum drug concentrations to fall below the minimum inhibitory concentration. Extending the dosing interval of an antimicrobial agent that has a PAE has several potential advantages, among them reduced cost, less toxicity, and better compliance among outpatients receiving antimicrobial therapy. Although data are limited, animal and human studies provide support for the clinical importance of the PAE. Further research into the impact of the PAE on antimicrobial dosing, efficacy, toxicity, and costs is warranted.

Animals↗
PubMed1992

Mathematic modeling of drug disposition and postdialysis rebound in patients requiring hemodialysis.

We developed a model to describe intradialysis and postdialysis serum concentration changes and, in concert with nonlinear regression, to estimate drug removal during hemodialysis. A Lotus-based computer simulation program was developed that describes drug disposition in this therapy. The hemodialysis removal rate constant and beta were two important factors identified that influence postdialysis rebound. Also, a nonlinear regression routine using PCNONLIN was developed that enables simultaneous fitting of predialysis, intradialysis, and postdialysis drug concentration data. Data from four patients who received intravenous sulbactam were analyzed using this model. The mean measured amount of sulbactam removed by hemodialysis was 446 +/- 32 mg versus predicted amounts of 456 +/- 92 mg from model estimates, and 449 +/- 33 mg when dialysate recovery of drug was included in the input. This program will be useful in characterizing pharmacokinetic constants and predicting hemodialysis drug removal.

Computer Simulation↗
PubMed1991

Theophylline toxicity secondary to ciprofloxacin administration.

We report the case of a 79-year-old woman who presented from a skilled nursing facility to the emergency department with signs and symptoms of theophylline toxicity and a serum theophylline concentration of 53.7 mg/L. The patient had been on a regular regimen of aminophylline for two months, with the addition of ciprofloxacin three days before arrival as the only identifiable potential cause of theophylline intoxication. She was monitored and treated conservatively with serial doses of activated charcoal, which resulted in a reduction of her serum theophylline level to a therapeutic concentration in 15 hours without adverse sequelae. The number of cases of theophylline intoxication secondary to concurrent ciprofloxacin administration is likely to increase, especially in nursing home populations, and it should be suspected when these patients present to the ED with the appropriate signs and symptoms. Management of theophylline intoxication should be based on clinical presentation as well as concentrations of the drug.

Aged↗
PubMed1991

Combined use of ciprofloxacin and sucralfate.

The effect of sucralfate on the bioavailability of ciprofloxacin hydrochloride was assessed in 12 healthy male volunteers. The study was a four-period crossover design where subjects were randomized to one of four treatment sequences at entry. Treatments A, B, and C included sucralfate 2 g q12h for five doses. For treatment A, the fifth dose sucralfate was administered concurrently with ciprofloxacin 750 mg. For treatment B, 750 mg of ciprofloxacin was administered two hours before the fifth dose of sucralfate. Treatment C consisted of ciprofloxacin 750 mg six hours before the fifth dose of sucralfate. A 750-mg dose of ciprofloxacin was administered alone for treatment D. Blood and urine samples were collected at predetermined time intervals for 24 hours. Ciprofloxacin concentrations were determined by HPLC. The area under the concentration versus time curve from zero to infinity and the urinary recovery of ciprofloxacin were used for determining relative bioavailability. Concurrent administration of ciprofloxacin and sucralfate (treatment A) resulted in a significant decrease (p less than 0.05) in ciprofloxacin absorption. The relative bioavailabilities for treatments A, B, and C were 0.0429 +/- 0.0202, 0.829 + 0.21, and 0.965 + 0.32, respectively, relative to ciprofloxacin alone. In normal volunteers, ciprofloxacin may be administered between two and six hours before sucralfate, allowing sufficient time for ciprofloxacin absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction. In patients with decreased gastric emptying the interaction may be more difficult to avoid.

Adolescent↗
PubMed1991

Use of antimicrobial drugs in adults before and after removal of a restriction policy.

The effects on the quantity and quality of antimicrobial drug use of removing an antimicrobial restriction policy are reported. Monthly totals for the number of courses of antimicrobial therapy and expenditures based on grams used were obtained from pharmacy records on adult inpatients for a portion (July-December 1987) of the restriction policy term and for the six months (July-December 1988) immediately after the policy ended. Data were obtained for nine restricted drugs and for three that were never restricted. Retrospective drug-use reviews were conducted for ceftazidime and imipenem-cilastatin. For the restricted agents, the total number of courses of therapy increased by 158% after the restriction policy was removed, and total expenditures increased by 103%. There were no significant changes in the number of courses of therapy or cost for the unrestricted antimicrobials. In the postrestriction period, ceftazidime and imipenem-cilastatin were used more often in patients who were less critically ill. Inappropriate use of imipenem-cilastatin occurred significantly more often after the restrictions were removed. Other factors potentially affecting the use of antimicrobials, such as patient age and the incidence of nosocomial infections, did not differ substantially between the two periods. The removal of an antimicrobial restriction policy resulted in increased use of and higher expenditures for previously restricted agents, as well as an increase in the inappropriate use of at least one agent.

Adult↗