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Keith A Rodvold

Publications and source records attributed to Keith A Rodvold.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacists' perceptions of the effectiveness of antimicrobial control programs.

PURPOSE: The perceptions of the effectiveness of antimicrobial control programs (ACPs) among infectious diseases (ID) pharmacists were studied. METHODS: A survey asking pharmacists to characterize the ACP in their hospitals and rate the program's effectiveness was distributed electronically in 1999 and by regular mail in 2000 to all 365 members of the Society of Infectious Diseases Pharmacists residing in North America. RESULTS: Of the 365 surveys distributed, 323 (88.5%) were completed, 233 of which were eligible for analysis. Most respondents (99%) indicated the use of one or more ACP components (mean +/- S.D., 4.3 +/- 1.9) in their hospitals. The ACP components used most frequently included prescriber education, review of patient medical records, formularies, prior authorization, infectious diseases consultation, and clinical practice guidelines. A similar percentage of respondents indicated that ID pharmacists and ID physicians directly participated in implementing and monitoring the effectiveness of ACPs (57% and 58%, respectively). Of the 231 respondents whose hospitals had an ACP, 73% perceived that their ACP effectively addressed antimicrobial resistance, patient outcomes, or costs, with cost reduction viewed as being accomplished more often than the improvement of patient outcomes or containment of antimicrobial resistance (62%, 35%, and 38%, respectively; p < 0.001). Many indicated uncertainty regarding the effectiveness of their ACP, with a substantial percentage of respondents believing that the level of support for these programs was inadequate. CONCLUSION: ID pharmacists in 231 North American hospitals perceived that their ACP was not sufficiently effective at improving patient outcomes, containing antimicrobial resistance, and decreasing medication costs, possibly due to inadequate institutional support for the program.

Anti-Infective Agents↗
PubMed2006

Serum, tissue and body fluid concentrations of tigecycline after a single 100 mg dose.

OBJECTIVES: The purpose of this study was to determine the tissue and corresponding serum concentration of tigecycline at selected time points in gall bladder, bile, colon, bone, synovial fluid (SF), lung and CSF in subjects undergoing surgical or medical procedures. METHODS: One hundred and four adult subjects (aged 24-83 years; 64 women, 40 men) received a single intravenous (i.v.) dose of tigecycline (100 mg infused over 30 min). Subjects were randomly assigned to one of four collection times at 4, 8, 12 and 24 h after the start of the infusion. For CSF, samples were collected at approximately 1.5 and 24 h after the start of the infusion. All subjects had serum samples collected before the administration of tigecycline, at the end of the infusion and at the time corresponding to tissue or body fluid collection. Drug concentrations in serum, tissues and body fluids were determined by LC/MS/MS. The area under the mean concentration-time curve from 0 to 24 h (AUC(0-24)) was determined for the comparison of systemic exposure between tissue or body fluid to serum. RESULTS: The mean serum concentrations of tigecycline were similar to those previously published. Tissue penetration, expressed as the ratio of AUC(0-24) in tissue or body fluid to serum, was 537 for bile, 23 for gall bladder, 2.6 for colon, 2.0 for lung, 0.41 for bone, 0.31 for SF and 0.11 for CSF. CONCLUSIONS: A single 100 mg dose of intravenous tigecycline produced considerably higher tissue/fluid concentrations in bile, gall bladder, colon and lung compared with simultaneous serum concentrations. On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations. The results in bone are inconsistent with previous radiolabelled studies in animals and it is unclear if tight binding to bone (versus low bone uptake) or poor extraction of tigecycline for LC/MS/MS detection or both may have contributed to the differences we observed in humans.

Adult↗
PubMed2006

Population pharmacokinetic modeling and Monte Carlo simulation of varying doses of intravenous metronidazole.

Population pharmacokinetic modeling and Monte Carlo simulation (MCS) are approaches used to determine probability of target attainment (PTA) of antimicrobial therapy. The objectives of this study were 1) to determine a population pharmacokinetic model (PPM) using metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients, and 2) to determine the probability of attaining the pharmacodynamic target area under the plasma concentration (AUC)/MIC ratio >or=70 against 218 clinical isolates of Bacteroides fragilis using MCS. Eighteen healthy subjects were randomized to 3 dosages of intravenous metronidazole (500 mg every 8 h, 1000 mg day(-1), 1500 mg day(-1)) in an open-label 3-way crossover fashion. Serial blood samples were collected over 25.5 h on the 3rd day of each study period. An additional of 8 critically ill patients received intravenous metronidazole 500 mg every 8 h. Serial blood samples were collected over 8 h after the 2nd day of dosing. Plasma metronidazole and hydroxy-metronidazole concentrations were analyzed using a high-performance liquid chromatographic assay. The 834 plasma concentrations from 62 data sets were simultaneously modeled with Non-Parametric Adaptive Grid population modeling program. A 4-compartment model with a metabolite and zero-order infusion into the central compartment was used. The mean parameter vector and covariance matrix from PPM were inserted into the simulation module of ADAPT II. A 10,000-subject MCS was performed to determine the probability of PTA for a total drug AUC to MIC ratio >or=70 against 218 isolates of B. fragilis (MIC range, 0.125-2.0 mg L(-1)). Mean parameter values were CL(non-OH), 3.08 L h(-1); Vc, 35.4 L; K(OH), 0.04 h(-1); CL(OH), 2.78 L h(-1); and V(OH), 9.66 L. The regression values of the observed versus predicted concentrations (r2) of metronidazole and hydroxy-metronidazole were 0.972 and 0.980, respectively. The PTA for metronidazole 1500 mg day(-1) or 500 mg every 8 h (taken together) and 1000 mg day(-1) were 99.9% and 99.8%, respectively, over the reported MIC distribution range. For an MIC of 4 mg L(-1), the predicted PTA decreased to 80.0% and 28.5%, respectively. A PPM was determined by comodeling metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients. Based on this model, attainment of the target pharmacodynamic parameter (AUC/MIC ratio >or=70) against B. fragilis isolates is >99% when MICs are <2 mg L(-1), irrespective of the dosing interval of 24 h.

Administration, Intravesical↗
PubMed2006

Antibiotic drug interactions.

Drug-drug interactions in the field of infectious diseases continue to expand as new drugs are approved, metabolic enzymes and transporters are identified, and recommendations for co-administration of drugs are revised. This article provides an overview of the principles and mechanisms of drug-drug interactions and describes pharmacokinetic-pharmacodynamic interactions commonly associated with antibacterial therapy, antiviral agents (non-retroviral), and drugs for tuberculosis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Daptomycin: a novel cyclic lipopeptide antimicrobial.

PURPOSE: The development, activity, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, and dosage and administration of daptomycin are reviewed. SUMMARY: Daptomycin, a novel cyclic lipopeptide antimicrobial, is bactericidal against a range of gram-positive bacteria, including many multiple-drug-resistant isolates. It has only minimal activity against anaerobic bacteria and no activity against gram-negative bacteria. Daptomycin exhibits linear pharmacokinetics, and the plasma concentration-versus-time relationship is best described by a two-compartment model with first-order elimination. The initial bactericidal activity is rapid, extensive, and concentration related. In clinical trials, daptomycin has shown efficacy in treating complicated skin and skin-structure infections (CSSSIs); the drug carries FDA-approved labeling for same. The adverse effects of daptomycin appear comparable to those of vancomycin and semisynthetic penicillins. The dosage for CSSSIs is 4 mg/kg by i.v. infusion every 24 hours. CONCLUSION: Daptomycin is bactericidal against gram-positive organisms and offers an option in the treatment of CSSSIs.

Anti-Bacterial Agents↗
PubMed2005

A clinician's guide to the appropriate and accurate use of antibiotics: the Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria.

In response to the overuse and misuse of antibiotics, leading to increasing bacterial resistance and decreasing development of new antibiotics, the Council for Appropriate and Rational Antibiotic Therapy (CARAT) has developed criteria to guide appropriate and accurate antibiotic selection. The criteria, which are aimed at optimizing antibiotic therapy, include evidence-based results, therapeutic benefits, safety, optimal drug for the optimal duration, and cost-effectiveness.

Anti-Bacterial Agents↗
PubMed2005

Levofloxacin plus metronidazole administered once daily versus moxifloxacin monotherapy against a mixed infection of Escherichia coli and Bacteroides fragilis in an in vitro pharmacodynamic model.

Moxifloxacin has been suggested as an option for monotherapy of intra-abdominal infections. Recent data support the use of a once-daily metronidazole regimen. The purpose of this study was to investigate the activity of levofloxacin (750 mg every 24 h [q24h]) plus metronidazole (1,500 mg q24h) compared with that of moxifloxacin (400 mg q24h) monotherapy in a mixed-infection model. By using an in vitro pharmacodynamic model in duplicate, Escherichia coli and Bacteroides fragilis were exposed to peak concentrations of 8.5 mg of levofloxacin/liter q24h, 32 mg of metronidazole/liter q24h, and 2 mg for moxifloxacin/liter q24h for 24 h. The activities of levofloxacin, metronidazole, moxifloxacin, and levofloxacin plus metronidazole were evaluated against E. coli, B. fragilis, and E. coli plus B. fragilis. The targeted half-lives of levofloxacin, metronidazole, and moxifloxacin were 8, 8, and 12 h, respectively. Time-kill curves were analyzed for time to 3-log killing, slope, and regrowth. Pre- and postexposure MICs were determined. The preexposure levofloxacin, metronidazole, and moxifloxacin MICs for E. coli and B. fragilis were 0.5 and 1, >64 and 0.5, and 1 and 0.25 mg/liter, respectively. Levofloxacin and moxifloxacin achieved a 3-log killing against E. coli and B. fragilis in all experiments, as did metronidazole against B. fragilis. Metronidazole did not decrease the starting inoculum of E. coli. The area under the concentration-time curve/MIC ratios for E. coli and B. fragilis were 171.7 and 85.9, respectively, for levofloxacin and 26 and 103.9, respectively, for moxifloxacin. Levofloxacin plus metronidazole exhibited the fastest rates of killing. The levofloxacin and moxifloxacin MICs for B. fragilis increased 8- to 16-fold after the organism was exposed to moxifloxacin. No other changes in the postexposure MICs were found. Levofloxacin plus metronidazole administered once daily exhibited activity similar to that of moxifloxacin against the mixed E. coli and B. fragilis infection. A once-daily regimen of levofloxacin plus metronidazole looks promising for the treatment of intra-abdominal infections.

Anti-Bacterial Agents↗
PubMed2004

Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration.

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.

Acetamides↗
PubMed2004

Pharmacokinetics and pharmacodynamics of intravenous levofloxacin at 750 milligrams and various doses of metronidazole in healthy adult subjects.

The purpose of this investigation was to evaluate the steady-state pharmacokinetics, pharmacodynamics, and safety of intravenous levofloxacin at 750 mg administered once daily combined with three different dosages of intravenous metronidazole (500 mg every 8 h [q8h], 1,000 mg q24h, and 1,500 mg q24h). Eighteen healthy adult subjects received all three combinations in a randomized, crossover fashion. Serial blood and urine samples were collected on the third day of each study period. The 24-h areas under the inhibitory (AUIC(0-24)) and bactericidal (AUBC(0-24)) curves of these three combination regimens were determined against clinical isolates of Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus asaccharolyticus, and Escherichia coli. The mean concentrations of levofloxacin were not different between study periods and were similar to those previously published. The mean (+/- standard deviation) areas under the metronidazole plasma concentration-time curve (AUC(0-24)) for 1,500-mg q24h (338 +/- 105 mg.h/liter) and 500-mg q8h (356 +/- 68 mg.h/liter) regimens were not different (P > 0.05), but both were significantly higher than the 1,000-mg q24h AUC(0-24) (P < 0.05, 227 +/- 57 mg.h/liter). Mean (+/- standard deviation) total body clearance and renal clearance values were similar among the 500-mg q8h, 1,000-mg q24, and 1,500-mg q24h regimens (62 +/- 7, 67 +/- 13, and 67 +/- 14 and 11 +/- 3, 12 +/- 2, and 12 +/- 5 ml/min/1.73 m2, respectively). Levofloxacin at 750 mg q24h plus metronidazole at 500 mg q8h or 1,500 mg q24h resulted in similar AUIC(0-24) and AUBC(0-24) values with one exception: the AUIC(0-24) for the 1,500-mg q24h regimen against B. thetaiotamicron was significantly higher (P < 0.05) than those of the other regimens. Overall, the combination of levofloxacin at 750 mg once daily and metronidazole at 500 mg q8h or 1,500 mg q24h appeared to have greater AUIC(0-24) and AUBC(0-24) values than did the 1,000-mg q24h regimen. All combination regimens of levofloxacin and metronidazole were well tolerated, and no serious drug-related adverse effects were reported. The pharmacokinetic, safety, and pharmacodynamic data from our study suggest that a once-daily regimen of intravenous levofloxacin at 750 mg and metronidazole at 1,500 mg warrants further clinical investigation.

Adolescent↗
PubMed2004

Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and Monte Carlo simulation.

The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was performed to estimate the probability of attaining a target free-piperacillin concentration greater than the MIC for 50% of the dosing interval for 3.375 g every 6 h or every 4 h given as a 0.5-h infusion at each MIC between 0.25 and 32 microg/ml. In the population pharmacokinetic analysis, measurements of bias and precision, observed-predicted plots, and r2 values were highly acceptable for all three models and all three models were appropriate candidates for the Monte Carlo simulation evaluation. Visual comparison of the distribution of the piperacillin concentrations at the pharmacodynamic endpoint--h 3 concentrations of a 6-h dosing interval--between the simulated populations and raw data revealed that the linear model was most reflective of the raw data at the pharmacodynamic endpoint, and the linear model was therefore selected for the target attainment analysis. In the target attainment analysis, administration of 3 g of piperacillin every 6 h resulted in a robust target attainment rate that exceeded 95% for MICs of < or =8 mg/liter. The 4-h piperacillin administration interval had a superior pharmacodynamic profile and provided target attainment rates exceeding 95% for MICs of < or =16 mg/liter. This study indicates that piperacillin-tazobactam should have utility for empirical therapy of hospital-onset infections.

Algorithms↗
PubMed2004

Fluctuations in vancomycin CNS tissue concentrations following intermittent and continuous infusions in the rat.

The purpose of this investigation was to compare the variability of vancomycin concentrations in the serum and CNS when administered continuously or as intermittent intravenous infusions in the rat. The hypothesis for this investigation was that the magnitude of change in serum vancomycin concentrations directly relates to the extent of vancomycin concentration fluctuations in the CNS. Microdialysis and serum sampling techniques were employed and biologic samples were analysed for vancomycin using HPLC. Over the dosing interval, the mean changes in concentrations were 71.8 +/- 9.8% and 13.6 +/- 9.3% for serum and 61.7 +/- 7.8% and 6.8 +/- 3.5% for brain extracellular fluid in the intermittent and continuously infused groups, respectively. Accordingly, the relative changes in vancomycin concentrations in brain extracellular fluid were closely associated with corresponding changes in serum concentrations (R2=0.94). Thus, continuous intravenous administration of vancomycin results in minimal serum and CNS tissue concentration changes as compared to traditional intermittent dosing methods and allows for more consistent vancomycin concentrations in the CNS.

Animals↗
PubMed2004

Sex-related differences in the pharmacokinetics of once-daily saquinavir soft-gelatin capsules boosted with low-dose ritonavir in patients infected with human immunodeficiency virus type 1.

STUDY OBJECTIVES: To compare the steady-state pharmacokinetics and safety of saquinavir soft-gelatin capsules (SGC) plus low-dose ritonavir administered once/day in antiretroviral-naive adult patients infected with the human immunodeficiency virus type 1 (HIV-1) and to evaluate any sex-related differences. DESIGN: Single-center, open-label, pharmacokinetic study. SETTING: University-affiliated outpatient HIV clinic. PATIENTS: Six men and seven women with HIV-1. INTERVENTION: Each patient received saquinavir SGC 1600 mg and ritonavir 100 mg for a 14-day course of therapy. Nine serial blood samples during 24 hours were collected on day 14 of therapy MEASUREMENTS AND MAIN RESULTS: Plasma saquinavir and ritonavir concentrations were measured by high-performance liquid chromatography. Standard noncompartmental methods were used to calculate the pharmacokinetic parameters. The unpaired Student t test was used for the statistical comparison of pharmacokinetic parameters between male and female patients. Once-daily saquinavir SGC plus ritonavir was generally well tolerated. Pharmacokinetic data from five men and five women were evaluable. The median saquinavir area under the concentration-time curve from 0-24 hours (AUC0-24) in the female patients (82,300 ng x hr/ml) was significantly (p=0.036) higher than that in the male patients (47,400 ng x hr/ml). This relationship remained significant for weight-adjusted saquinavir AUC0-24 values. Ritonavir's apparent oral clearance in the women was significantly (p=0.023) lower than that in the men. CONCLUSION: Significantly higher plasma concentrations of saquinavir were achieved in female compared with male HIV-infected patients receiving once-daily saquinavir SGC 1600 mg plus ritonavir 100 mg.

Adult↗
PubMed2004

Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects.

This report details the findings of a single-dose Phase I pharmacokinetic and toxicity study of a food-based formulation of lycopene in healthy adult male subjects. Five dosing groups (n = 5 per group) were sequentially treated with increasing doses of lycopene ranging from 10 to 120 mg. Blood samples were collected for a total of 28 days (672 h) after administration of single doses of lycopene. The mean time (t(max)) to reach maximum total lycopene concentration (C(max)) ranged from 15.6 to 32.6 h. The C(max) for total lycopene ranged between 4.03 and 11.27 microg/dl (0.075-0.210 microm). Mean AUC(0-96) and elimination half-life for total lycopene ranged from 214 to 655 microg h/dl (3.986-12.201 micromol h/l) and 28.1 and 61.6 h, respectively. The changes observed in lycopene exposure parameters (e.g., C(max) and AUC(0-96)) were not proportional to increments in dose, with larger increases observed at the lowest end of the dosing range (10-30 mg). Chylomicron lycopene was measured during the first 12 h with the differences observed among the dosing groups not reaching statistical significance. These findings may reflect a process of absorption that is saturable at very low dosing levels or may be explained by the large interindividual variability in attained lycopene concentrations that were observed within each dosing group. Pharmacokinetic parameters for trans- and cis-lycopene isomers were calculated and are reported here. The formulation was well tolerated with minimal side effects, which were mainly of gastrointestinal nature and of very low grade.

Administration, Oral↗
PubMed2003

Steady-state plasma and bronchopulmonary characteristics of clarithromycin extended-release tablets in normal healthy adult subjects.

OBJECTIVES: The steady-state concentrations of clarithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL). Concentrations of the major metabolite, 14-hydroxyclarithromycin, were also determined in plasma and AM. MATERIALS AND METHODS: Forty-two healthy, non-smoking adult subjects (age: 18-54 years; 19 females, 23 males) received oral clarithromycin extended-release formulation (1000 mg once daily for five consecutive days). Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, 24 or 48 h after the last administered dose of clarithromycin. In addition, three subjects who did not take clarithromycin served as controls and underwent bronchoscopy at 0 h. Drug concentrations in plasma, ELF, and AM were determined by high-performance liquid chromatography. RESULTS: Clarithromycin was extensively concentrated in ELF [range of mean (+/-s.d.) concentrations: 6.38 +/- 3.92 to 11.50 +/- 6.65 mg/L] and AM (127.0 +/- 61.5 to 573.8 +/- 309.3 mg/L) than simultaneous plasma concentration (0.75 +/- 0.31 to 2.22 +/- 0.72 mg/L). The ranges of mean (+/-s.d.) concentrations of 14-hydroxyclarithromycin in plasma and AM were 0.52 +/- 0.29 to 0.80 +/- 0.31 mg/L and 22.1 +/- 13.5 to 49.5 +/- 16.2 mg/L, respectively. CONCLUSIONS: Once-daily dosing of extended-release formulation clarithromycin 1000 mg produced significantly (P < 0.05) higher steady-state concentrations of clarithromycin in ELF (2-14 times) and AM (50-700 times) compared to simultaneous plasma concentrations throughout the 24 h period after drug administration. The 14-hydroxy metabolite of clarithromycin achieved significantly (P < 0.05) higher steady-state concentrations in AM (18-180 times) compared with concurrent plasma concentrations.

Adult↗
PubMed2003

A physiological pharmacokinetic model describing the disposition of lycopene in healthy men.

A physiological pharmacokinetic model was developed to describe the disposition of lycopene, delivered as a tomato beverage formulation in five graded doses (10, 30, 60, 90, or 120 mg), for a phase I study in healthy male subjects (five per dose). Blood was collected before dose administration (0 h) and at scheduled intervals until 672 h. Serum concentrations of carotenoids and vitamins were measured by high performance liquid chromatography analysis. The model was comprised of seven compartments: gastrointestinal tract, enterocytes, chylomicrons, plasma lipoproteins, fast-turnover liver, slow-turnover tissues, and a delay compartment before the enterocytes. As predicted, the percent absorption at the 10 mg dose (33.9 +/- 8.1%) was significantly greater than at the higher doses; however, the amount of lycopene absorbed (mg) was not statistically different (mean: 4.69 +/- 0.55 mg) between doses, suggesting a possible saturation of absorptive mechanisms. The slow-turnover tissue compartment served as a slow-depleting reservoir for lycopene, and the liver represented the fast-turnover pool. Independent of dose, 80% of the subjects absorbed less than 6 mg of lycopene. This may have important implications for planning clinical trials with pharmacological doses of lycopene in cancer control and prevention if absorption saturation occurs at levels that are already being consumed in the population.

Adult↗
PubMed2003

Safety and tolerability of fluoroquinolones.

Clinical trials in patients with community- and hospital-acquired infections have established that the clinical effectiveness and safety of fluoroquinolones are similar to beta-lactam and macrolide agents. The most common drug-related adverse effects (AEs) with fluoroquinolone therapy involve the gastrointestinal tract and central nervous system and are usually transient and mild to moderate in severity. However, serious toxic reactions have led to the limited and restrictive use of trovafloxacin in the United States and the withdrawal of temafloxacin and grepafloxacin from worldwide markets. In addition, postmarketing spontaneous AE reports have imposed updates in the precautions and warning sections of product package inserts of selected fluoroquinolones. This article reviews the AEs associated with the fluoroquinolones and compares the safety profiles of ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin.

Anaphylaxis↗
PubMed2003

Pharmacokinetics and tissue distribution of orally administered lycopene in male dogs.

Consumption of lycopene, the predominant carotenoid in tomatoes and tomato products, is associated with reduced prostate cancer risk. The purpose of this study was to measure the pharmacokinetics and tissue distribution of lycopene after oral administration to male dogs. After single doses of 10, 30 and 50 mg/kg body weight (BW) lycopene to 2 dogs/dose, the mean half-life was 36 h and the plasma systemic exposure levels (AUC(0-)( infinity ), area under the curve) after the 30 and 50 mg/kg BW doses were similar. In a repeat dose study, 30 mg/(kg BW. d) administered orally to six dogs for 28 d resulted in steady-state plasma concentrations between 785 and 997 nmol/L lycopene. Apparent clearance, volume of distribution and apparent elimination half-life were 2.29 L/(h. kg), 96 L/kg and 30.5 h, respectively. Dogs were killed 1 or 5 d after the last dose and 23 tissues were collected for lycopene analysis. Lycopene concentrations were highest in liver, adrenals, spleen, lymph nodes and intestinal tissues. Liver lycopene concentrations were 66 and 91 nmol/g 1 and 5 d after cessation of treatment, respectively. Prostate lycopene concentrations were < 0.2 nmol/g both 1 and 5 d after dosing ceased (<0.4% of liver concentrations). Although 70% trans-lycopene was used in the dosing material, most of the lycopene identified in plasma and tissues was cis-lycopene.

Administration, Oral↗