Biomedical subjects

M Nadai

Publications and source records attributed to M Nadai.

At least 19 recordsLinked to original sources

PubMed2000

End-of-life decisions in neonatal intensive care: physicians' self-reported practices in seven European countries. EURONIC Study Group.

BACKGROUND: The ethical issue of foregoing life-sustaining treatment for newborn infants at high risk of death or severe disability is extensively debated, but there is little information on how physicians in different countries actually confront this issue to reach end-of-life decisions. The EURONIC project aimed to investigate practices as reported by physicians themselves. METHODS: The study recruited a large, representative sample of 122 neonatal intensive-care units (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified random sampling (in France, Germany, the UK, Italy, and Spain) with an overall response rate of 86%. Physicians' practices of end-of-life decision-making were investigated through an anonymous, self-administered questionnaire. 1235 completed questionnaires were returned (response rate 89%). FINDINGS: In all countries, most physicians reported having been involved at least once in setting limits to intensive care because of incurable conditions (61-96%); smaller proportions reported such involvement because of a baby's poor neurological prognosis (46-90%). Practices such as continuation of current treatment without intensification and withholding of emergency manoeuvres were widespread, but withdrawal of mechanical ventilation was reported by variable proportions (28-90%). Only in France (73%) and the Netherlands (47%) was the administration of drugs with the aim of ending life reported with substantial frequency. Age, length of professional experience, and the importance of religion in the physician's life affected the likelihood of reporting of non-treatment decisions. INTERPRETATION: A vast majority of neonatologists in European NICUs have been involved in end-of-life limitation of treatments, but type of decision-making varies among countries. Culture-related and other country-specific factors are more relevant than characteristics of individual physicians or units in explaining such variability.

Adult↗

PubMed2000

Lincomycin-induced endotoxin release in Escherichia coli sepsis: evidence for release in vitro and in vivo.

OBJECTIVE: To evaluate the propensity of lincomycin and clindamycin to induce release of endotoxin, the authors investigated endotoxin release in Escherichia coli isolated from a patient who developed septic shock following lincomycin treatment. METHODS: Endotoxin release from the E. coli isolate exposed to lincomycin, clindamycin, and ceftazidime were determined in vitro and in vivo. RESULTS: In vitro, this E. coli released significantly larger amounts of endotoxin after exposure for 6 hours to lincomycin or clindamycin versus no antibiotic; however, endotoxin release with these antibiotics was significantly less than with ceftazidime. There was no significant difference in in vitro endotoxin release between small (8 mg/L) and large (0.5 minimum inhibitory concentration [MIC]) doses of these antibiotics, and 0.5 MICs of lincomycin and clindamycin were 1024 and 256 mg/L, respectively. These results were supported by scanning electron microscopic observations, which demonstrated that lincomycin, clindamycin, and ceftazidime induced formation of filamentous cells. In addition, plasma endotoxin concentrations after treatment for 4 hours with lincomycin, clindamycin, and ceftazidime (5 mg/kg) were at least 20-fold higher than with no antibiotic in an E. coli sepsis rat model. CONCLUSION: Results of this study suggest that the bacteriostatic antibiotics, lincomycin and clindamycin, induce endotoxin release in the treatment of E. coli infections.

Animals↗

PubMed2000

Changes in absorptive function of rat intestine injured by methotrexate.

1. Methotrexate (MTX), an anticancer drug, has been shown to induce acute injury in the small intestine. The present study was designed to investigate the in vivo absorptive function of the small intestine injured by MTX using an amino-beta-lactam antibiotic cephalexin (CEX). Time-dependent changes in diamine oxidase (DAO) and alkaline phosphatase (ALP) activity in the small intestine and histopathological findings were also measured in rats treated with MTX (20 mg/kg). 2. Most severe mucosal damage was observed 2 days after MTX treatment and the area under the plasma concentration-time curve of CEX (AUC(CEX)) following oral administration of 20 mg/kg tended to decrease. Thereafter, the AUC(CEX) increased significantly and the histopathological changes diminished within 5 days. 3. Both villus height and mucosal weight followed the same pattern, decreasing in the first 2 or 3 days following treatment, increasing on the 5th day and returning to control levels by the 10th day. Methotrexate-induced changes in the mucosal wet weight/whole intestinal weight ratio were significantly correlated with those of AUC(CEX), but did not correlate with mucosal DAO and ALP activity. 4. These findings provide evidence that the change in the total amount of CEX is an index of the active transport function, probably by intestinal peptide transporter (PEPT1), and is well reflected by histopathological changes in the intestinal mucosa induced by MTX. In addition, there is a possibility that this method could be applied in the clinical setting for diagnosis of intestinal status and absorptive function.

Alkaline Phosphatase↗

PubMed2000

Treatment choices for extremely preterm infants: an international perspective.

OBJECTIVE: To compare treatment choices of neonatal physicians and nurses in 11 European countries for a hypothetical case of extreme prematurity (24 weeks' gestational age, birth weight of 560 g, Apgar score of 1 at 1 minute). STUDY DESIGN: An anonymous, self-administered questionnaire was completed by 1401 physicians (response rate, 89%) and 3425 nurses (response rate, 86%) from a large, representative sample of 143 European neonatal intensive care units. Italy, Spain, France, Germany, the Netherlands, Luxembourg, Great Britain, Sweden, Hungary, Estonia, and Lithuania participated. RESULTS: Most physicians in every country but the Netherlands would resuscitate this baby and start intensive care. On subsequent deterioration of clinical conditions caused by a severe intraventricular hemorrhage, attitudes diverge: most neonatologists in Germany, Italy, Estonia, and Hungary would favor continuation of intensive care, whereas in the other countries some form of limitation of treatment would be the preferred choice. Parental wishes appear to play a role especially in Great Britain and the Netherlands. Nurses are more prone than doctors to withhold resuscitation in the delivery room and to ask parental opinion regarding subsequent treatment choices. CONCLUSION: An extremely premature infant is regarded as viable by most physicians, whereas after deterioration of the clinical conditions decision-making patterns vary according to country. These findings have implications for the ethical debate surrounding treatment of infants of borderline viability and for the interpretation and comparison of international statistics.

Adult↗

PubMed1999

Decreased antipyrine clearance following endotoxin administration: in vivo evidence of the role of nitric oxide.

Klebsiella pneumoniae endotoxin has been found to decrease hepatic P450-mediated drug-metabolizing enzyme activity in a time-dependent manner. In this study, we investigated the role of nitric oxide (NO) in the decrease in hepatic drug-metabolizing enzyme activity caused by endotoxin in vivo. We measured in vivo pharmacokinetic parameters of antipyrine in rats treated with endotoxin and/or a selective inhibitor of inducible NO synthase (iNOS), S-methylisothiourea. Intraperitoneal injection of endotoxin (1 mg/kg of body weight) dramatically decreased the systemic clearance of antipyrine, reflecting reduced hepatic drug-metabolizing enzyme activity, and significantly increased the level of nitrite and nitrate (NOx) in the plasma. S-Methylisothiourea (10 mg/kg) reversed this decreasing antipyrine clearance and reduced the level of NOx in plasma. Repeated injections of an NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK-409; 10 mg/kg), at a dose which maintained plasma NOx at the same levels as those caused by endotoxin injection, also decreased the systemic clearance of antipyrine. These findings suggest that the overproduction of NO observed in this animal model is at least partially responsible for the significant reduction in the hepatic drug-metabolizing enzyme activity that may happen in a gram-negative bacterial infection.

Animals↗

PubMed1998

Carbapenem-induced endotoxin release in gram-negative bacterial sepsis rat models.

The carbapenem-induced endotoxin release was evaluated using experimental models of gram-negative bacterial sepsis in Wistar rats. Infections with Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus vulgaris and Proteus mirabilis resulted in an increase of the plasma endotoxin concentration after treatment with ceftazidime and carbapenems including imipenem, panipenem, meropenem and biapenem. Except for P. aeruginosa, the plasma endotoxin concentrations after carbapenem treatment were significantly lower than those after ceftazidime treatment. It is noteworthy that treatment of P. aeruginosa sepsis with meropenem or biapenem induced significantly more endotoxin release than other carbapenems and the endotoxin concentrations induced by these carbapenems reached those of ceftazidime treatment. The plasma endotoxin concentrations appeared to correlate with the reduction of platelet counts and the elevation of both glutamic oxaloacetic transaminase and glutamic pyruvic transaminase values.

Animals↗

PubMed1998

Time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic drug-metabolizing enzyme activity in rats.

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b5 content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mg kg(-1)) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mg kg(-1)) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor alpha (TNFalpha) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFalpha produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFalpha is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1.0 mgkg(-1)K. pneumoniae endotoxin in rats reduces hepatic P450 and b5 levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.

Animals↗

PubMed1998

Possible mechanism by which the carbapenem antibiotic panipenem decreases the concentration of valproic acid in plasma in rats.

There is evidence indicating that the carbapenem antibiotic panipenem decreases plasma concentrations of valproic acid (VPA) in epileptic patients during VPA therapy. The mechanism for panipenem-induced changes in the pharmacokinetics of VPA was investigated in rats with and without bile duct cannulation. The effect of panipenem on the pharmacokinetics of diclofenac, which undergoes extensive enterohepatic recirculation, was also examined. VPA (50 mg/kg of body weight) or diclofenac (10 mg/kg of body weight) was administered intravenously under the steady-state plasma panipenem concentration of 4 microgram/ml, which had been achieved by a constant infusion rate. Panipenem decreased the plasma VPA concentrations in rats without bile duct cannulation but did not change the volume of the initial space and protein binding of VPA. However, panipenem had no effect on the plasma VPA concentrations and the biliary excretion of VPA in rats with bile duct cannulation. The secondary increase in plasma diclofenac concentration observed in the absence of panipenem was diminished in the presence of panipenem. These findings suggest that panipenem decreases plasma VPA concentrations by suppressing its enterohepatic recirculation, probably due to a panipenem-induced decrease in the numbers of enteric bacteria.

Animals↗

PubMed1998

Granulocyte colony-stimulating factor enhances endotoxin-induced decrease in biliary excretion of the antibiotic cefoperazone in rats.

We have recently reported that endotoxin (lipopolysaccharide [LPS]) derived from Klebsiella pneumoniae dramatically decreased the biliary excretion of the beta-lactam antibiotic cefoperazone (CPZ), which is primarily excreted into the bile via the anion transport system, in rats. The present study was designed to investigate the effect of human recombinant granulocyte colony-stimulating factor (G-CSF), which is reported to be beneficial in experimental models of inflammation, on the pharmacokinetics and biliary excretion of CPZ in rats. CPZ (20 mg/kg of body weight) was administered intravenously 2 h after the intravenous injection of LPS (250 microgram/kg). G-CSF was injected subcutaneously at 12 microgram/kg for 3 days and was administered intravenously at a final dose of 50 microgram/kg 1 h before LPS injection. Peripheral blood cell numbers were also measured. LPS dramatically decreased the systemic and biliary clearances of CPZ and the bile flow rate. Pretreatment with G-CSF enhanced these decreases induced by LPS. The total leukocyte numbers were increased in rats pretreated with G-CSF compared to the numbers in the controls, while the total leukocyte numbers were decreased (about 3,000 cells/microliter) by treatment with LPS. Pretreatment with G-CSF produces a deleterious effect against the LPS-induced decrease in biliary secretion of CPZ, and leukocytes play an important role in that mechanism.

Animals↗

PubMed1997

Cyclosporine therapy affects aminotransferase activity but not hepatitis C virus RNA levels in chronic hepatitis C.

Interferon (IFN) therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and is often limited by side effects. Cyclosporine A (CsA) is a potent immunosuppressant widely used in organ transplantation. We conducted a pilot study to determine whether CsA therapy could affect aminotransferase activity and hepatitis C virus RNA levels in patients with chronic hepatitis C. Cyclosporine A was administered to 10 patients (mean age of 59 years; male:female = 9:1) who did not respond to IFN therapy previously and who had elevated serum alanine aminotransferase (ALT) values for at least 6 months. All patients were positive for HCV-RNA by RT-PCR with genotype 1b. Their mean duration of hepatitis was 15 years. Oral CsA was given for 3 months in a dose that was increased at 1 month intervals from 1.5-2.0 to 2.0-3.0 and 3.0-4.0 mg/kg per day. All patients completed the treatment schedule, although two patients developed mild non-symptomatic hypertension. Serum ALT levels gradually decreased in all but one patient. The mean percentage decrease was 59.5% at the end of therapy (from 153 +/- 82 to 62 +/- 48 IU/L; P < 0.02). The ALT levels fell to the normal range in five patients, although once therapy was discontinued the enzyme levels tended to return to pretreatment levels. Serum aspartate aminotransferase and g-glutamyl transpeptidase levels similarly decreased. The serum HCV-RNA titre, determined by competitive RT-PCR, did not change in any patient throughout the study period. There were no appreciable alterations in other laboratory tests, such as serum creatinine levels and lymphocyte subsets, except for an increase in serum alkaline phosphatase levels. These findings suggest that CsA, even in a relatively low dose, reduces serum aminotransferase levels without serious side effects in patients with chronic hepatitis C, although an antiviral effect was not noted.

Administration, Oral↗

PubMed1997

Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis.

The present work was designed to elucidate the in vivo role of complement in the proteinuria-associated tubulointerstitial injury. Rats were intravenously injected with puromycin aminonucleoside, and massive proteinuria was observed within 5 days. Prominent tubulointerstitial injury characterized by proximal tubular degeneration, tubular dilatation, and leukocyte infiltration were observed 7 days after injection. C3 and C5b-9 were observed in the luminal side of proximal tubular cells. Renal function, assessed by inulin and para-aminohippurate clearance, was significantly decreased. To-assess the role of complement in this model, rats were injected with either cobra venom factor or soluble recombinant human complement receptor type 1 starting at day 3. These manipulations significantly improved tubulointerstitial pathology and para-aminohippurate clearance without affecting the degree of proteinuria. Deposition of C3 and C5b-9 was not detected in the kidney of rats depleted of complement by cobra venom factor. In rats treated with soluble complement receptor, C3 was still detected in the tubules, but deposition of C5b-9 was not observed. Soluble complement receptor was detected at the site of C3 deposition and in the urine. These data strongly suggest that complement plays a pivotal role in proteinuria-associated tubulointerstitial injury and that systemic complement depletion or inhibition of complement in the tubular lumen may diminish the tubulointerstitial damage.

Animals↗

PubMed1996

Dysfunction of cholinergic and dopaminergic neuronal systems in beta-amyloid protein--infused rats.

Accumulations of beta-amyloid protein are characteristic and diagnostic features of the brain of Alzheimer's disease patients; however, the physiological role of this protein in CNS is unknown. We have previously reported that continuous infusion of beta-amyloid protein into rat cerebral ventricle impairs learning ability and decreases choline acetyltransferase activity, a marker enzyme of cholinergic neuron. In this study, the effects of beta-amyloid protein infusion on the release of neurotransmitters in cholinergic and dopaminergic neuronal systems were investigated by using an in vivo brain microdialysis method. Nicotine-stimulated release of acetylcholine and dopamine in these animals was significantly lower than that in vehicle-infused rats. Further, dopamine release induced by high-K stimulation was decreased in beta-amyloid protein-infused rats compared with vehicle-infused rats. These results suggest that the release of the two transmitters, acetylcholine and dopamine, was decreased by beta-amyloid protein and that learning deficits observed in the beta-amyloid protein-infused rats are partly due to the impairment of neurotransmitter release. Furthermore, continuous infusion of beta-amyloid protein may be a useful method to produce the animal model of Alzheimer's disease.

Acetylcholine↗

PubMed1996

Clinical application of the Biotrack 516 system for determination of theophylline by a turbidimetric latex agglutination inhibition reaction.

Several automated analytical systems for therapeutic drug monitoring (TDM) have been developed. In the present study, theophylline concentration in plasma was measured by the Biotrack 516 system for theophylline, a newly developed automated system based on the turbidimetric latex agglutination inhibition reaction, using whole blood samples obtained from 35 asthmatic patients receiving chronic theophylline therapy. The data were compared with those obtained by high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA). Within-day and between-day precisions for the Biotrack system using blood samples obtained from nine patients ranged from 4.1 to 5.8% and from 2.0 to 6.2%, respectively. Comparison of this system with HPLC and FPIA methods indicated good correlation coefficients of > 0.960, while the respective slope and intercept did not differ from unity and zero. No cross-reactivity of this system with the main metabolites of theophylline and caffeine was observed, thus indicating that the antibodies possess specificity for theophylline. These findings suggest that the Biotrack-516 system is a method that enjoys both accuracy and precision to the same degree as established methods and hence will prove useful in the routine monitoring of plasma theophylline concentrations.

Anti-Asthmatic Agents↗

PubMed1996

Alterations in renal uptake kinetics of the xanthine derivative enprofylline in endotoxaemic mice.

The pharmacokinetics and renal uptake of enprofylline, which is primarily excreted into the urine by an active tubular secretion mechanism, were investigated in endotoxaemic mice by lipopolysaccharide isolated from Klebsiella pneumoniae. Lipopolysaccharide (1 mg kg-1) was infused 2 h before starting the examination, thereby inducing a decrease in the systemic clearance and an increase in the steady-state volume of distribution of enprofylline while inducing no changes in the urinary recovery (> 90%). The protein binding of enprofylline significantly decreased in the presence of lipopolysaccharide. Both the systemic clearance for unbound enprofylline and glomerular filtration rate decreased in the treated mice. A nonlinear relationship was found in both groups between the steady-state unbound plasma concentration and renal uptake of enprofylline after constant infusion for 1 h. The renal uptake rate of enprofylline decreased in the treated mice. Lipopolysaccaharide caused increases in the apparent maximum capacity for renal uptake (Vmax) from 17.3 to 32.2 micrograms h-1 g-1 of kidney and in the Michaelis-Menten constant (Km) from 2.7 to 21.7 micrograms mL-1 and decrease in the nonsaturable uptake rate constant (K4) from 0.87 to 0.43 mL h-1 g-1 of kidney. These results indicate that lipopolysaccharide decreases the renal tubular secretion of enprofylline by inducing a decrease in the renal uptake ability.

Animals↗

PubMed1995

Brain distribution characteristics of xanthine derivatives and relation to their locomotor activity in mice.

The relationship between the brain distribution and motor activity in mice of the xanthines, theophylline, enprofylline, 1-methyl-3-propylxanthine (MPX) and oxpentifylline was investigated. Their plasma protein binding and hydrophobicity were also examined. When these xanthines were administered orally, enprofylline and oxpentifylline had no effect on motor activity. While theophylline increased motor activity over 10 mg kg-1, MPX caused a decrease in such activity over 10 mg kg-1. The protein-binding behaviour varied among these xanthines and was closely related to their hydrophobicity, which is represented as a logarithmic partition coefficient (log PC). MPX had the highest hydrophobicity, while oxpentifylline had the lowest. Brain distribution characteristics varied among these xanthines, with the rank order of their brain penetration ratio, calculated as the ratio of brain to unbound plasma concentrations, being theophylline > oxpentifylline > MPX > enprofylline. The inhibition constants (Ki) for adenosine A1 receptors and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase (PDE) of these xanthines were 44.6 and 134, > 1000 and 112, 26.4 and 49, and > 1000 and 111 microM for theophylline, enprofylline, MPX, and oxpentifylline, respectively. These findings suggest that the lack of effects of enprofylline and oxpentifylline on motor activity is probably due to their low brain penetration ratio or low adenosine A1 affinity in comparison with theophylline. The decrease in the motor activity by MPX may be, in part, mediated by cAMP or adenosine.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1995

Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats.

Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the beta-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion.

Aging↗

PubMed1995

Effect of a bacterial lipopolysaccharide on biliary excretion of a beta-lactam antibiotic, cefoperazone, in rats.

Klebsiella pneumoniae O3 lipopolysaccharide (LPS) has been found to dramatically modify the pharmacokinetics of the beta-lactam antibiotic cefazolin in rats. This study investigated the effect of LPS on the biliary excretion of the beta-lactam antibiotic cefoperazone (CPZ) in rats. CPZ is known to be actively secreted into the bile by a carrier-mediated transport system. LPS (250 micrograms/kg of body weight) was infused for 20 to 30 min 2 h before an intravenous administration of CPZ (20 mg/kg). The pharmacokinetic parameters of CPZ were estimated by a noncompartment model. LPS induced a significant decrease in the systemic clearance (by approximately 50%) and an increase in the mean residence time of CPZ. Significant decreases were also seen in the bile flow rate and in the biliary recovery of unchanged CPZ in the LPS-treated rats. LPS tended to increase the proportion of urinary excretion of CPZ. LPS significantly decreased the biliary clearance (by approximately 55%) and renal clearance (by approximately 35%) of CPZ. However, no changes in the volume of distribution at steady state for CPZ were observed between the treatment groups. Our findings suggest that LPS induces changes in the pharmacokinetics of CPZ as a result of changes occurring in the biliary secretory system.

Animals↗

PubMed1995

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.

The effects of single coadministrations of one of three traditional Chinese medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy volunteers in an open, random crossover fashion. Subjects each received a single oral dose of LVFX (200 mg) alone and then with a single coadministration of each Chinese medicine. There were no significant differences in any pharmacokinetic parameters of LVFX between the groups. Also, no significant changes in the urinary recovery (> 80%) and renal clearance of LVFX were observed. These results indicate that the Chinese medicines tested have no significant effect on the rate and extent of bioavailability or renal excretion of LVFX.

Adult↗