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Biomedical subjects

R C Li

Publications and source records attributed to R C Li.

At least 37 records · Page 2Linked to original sources
PubMed1999

Triterpene antioxidants from ganoderma lucidum.

Ganoderma lucidum was studied for its antioxidative activity by bioassay guided isolation in conjunction with in vitro tests. The powdered crude drug was treated with boiling water and the aqueous extract (Ex1) was further separated to obtain terpene and polysaccharide fractions. The two fractions and Ex1 were screened for their antioxidative effect against pyrogallol induced erythrocyte membrane oxidation and Fe (II)-ascorbic acid induced lipid peroxidation. All tested samples showed antioxidative activities in a dose dependent manner and the terpene fraction was found to possess the highest effect compared with the others. Chemical isolation of the terpene fraction resulted in the detection of ganoderic acids A, B, C and D, lucidenic acid B and ganodermanontriol as major ingredients.

Animals↗
PubMed1999

Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model.

To evaluate the potential activity of Schisandra chinensis in restoring hepatic drug metabolism in CCl4 damaged liver, antipyrine was employed as a probe for the possible effects of the herb on Phase I oxidative metabolism in rats. Schisandra lignan fraction (160 mg/kg) was given orally to male Sprague-Dawley rats (220-240 g) 30 min or 6 h before CCl4 intoxication (4 ml/kg, s.c.). Following a single oral dose of antipyrine (80 mg/kg) to the rats with damaged liver, the pharmacokinetics of antipyrine in whole blood were determined and levels of liver enzymes, e.g. SGPT, SGOT, and cytochrome P450 were measured. Pharmacokinetic parameters for antipyrine were estimated using noncompartmental analysis. Results indicated that CCl4 significantly increased the elimination half-life (t(1/2)) of antipyrine from 2.59 +/- 1.04 to 11.25 +/- 3.91 h (P < 0.001) and decreased its clearance (CL) from 65.94 to 10.84 ml/h as compared to control. Pretreatment with the Schisandra lignan fraction 30 min or 6 h before intoxication significantly (P < 0.001) improved antipyrine elimination by reducing its t(1/2) to 3.30 +/- 0.52 and 3.58 +/- 1.05 h, respectively. The corresponding improvements observed for CL, i.e. 49.06 +/- 21.75 ml/h (P < 0.01); 21.10 +/- 10.42 ml/h (P < 0.05), were also substantial. Moreover, normalization of SGPT, SGOT and P450 levels was observed with the two Schisandra pretreatment schedules. In conclusion, Schisandra lignans exhibited strong protective effect on Phase I oxidative metabolism in the liver damaged by CCl4. Furthermore, pretreatment of Schisandra 30 min before intoxication showed a more pronounced effect than that of the 6 h pretreatment. The current pharmacokinetic approach allowed the protective effects of Schisandra on oxidative drug metabolism in damaged liver to be systemically examined and will certainly help in the evaluation of hepato-protectants obtained from natural sources.

Animals↗
PubMed1999

Effects of taraxacum mongolicum on the bioavailability and disposition of ciprofloxacin in rats.

Taraxacum mongolicum (TM), also known as dandelion, is a herb widely used in the East for its antibacterial activity. The high mineral content of TM presents a potential problem for the absorption of quinolone antibiotics. This study was undertaken to discern the significance of a drug-drug interaction between TM and ciprofloxacin. Two groups of Sprague Dawley rats (220-250 g) were employed; one received a single oral dose of ciprofloxacin (20 mg/kg) with concomitant oral administration of an aqueous TM extract (2 g crude drug/kg) while the control group received oral ciprofloxacin (20 mg/kg) only. Ciprofloxacin in plasma and urine, collected over 6 and 24 h, respectively, was determined by HPLC. Noncompartment analysis was employed for pharmacokinetic parameter estimation. Results indicated that, as compared to control, maximum plasma concentration (Cmax) of ciprofloxacin was significantly lowered by 73% in rats receiving concurrent TM dosing. Oral TM also caused a 3-fold increase in both apparent drug distribution volume (Vd,lambdaz/F: 92. 0 vs 30.8 L/kg) and terminal elimination half-life (t1/2,lambdaz; 5. 71 vs 1.96 h). Partly due to the changes in drug distribution and elimination, relative bioavailability of ciprofloxacin, as assessed by AUC0-->infinity, remained similar for both dosing groups. These findings suggest the possibility of a multifactorial drug-drug interaction between TM and ciprofloxacin. Thus, the implications of concomitant dosing of the two agents should not be overlooked.

Animals↗
PubMed1999

Netilmicin pharmacokinetics in Hong Kong Chinese cancer patients.

OBJECTIVES: To study the pharmacokinetics of netilmicin in Chinese haematology-oncology patients and to determine the pharmacokinetic differences, if any, between this patient subpopulation of Chinese and Caucasians. METHODS: A prospective study was carried out in the adult oncology unit of a major hospital in Hong Kong. During a 6 week period in 1997, all patients commencing on netilmicin therapy were monitored; the patients' demographics, clinical status, netilmicin dose and regimen, and drug administration/blood sampling time were collected. Pharmacokinetic parameters were generated using the USC*PACK package based on specifics of the patients themselves and Caucasians matched for the same patients' parameters using the Bayesian alogrithms. RESULTS: A total of 22 patients were enrolled into the study. Twenty-nine sets of levels were drawn, but only 25 sets from 18 patients (86%) were interpretable. The predicted peak (7.47+/-1.46 microg ml-1 ) and trough levels (1.39+/-0.96 microg ml-1 ) generated by USC*PACK were found to be significantly higher than the levels observed (6.01+/-1.14 microg ml-1 and 0.93+/-0.71 microg ml-1, respectively). Netilmicin clearance, volume of distribution and rate of elimination were all significantly higher in this Chinese subpopulation than those predicted for matched Caucasians. Conclusion Alterations in the netilmicin pharmacokinetics observed in our study population might be related to the disease state and/or ethics of the study patient population. Direct application of Caucasian based population pharmacokinetic parameters to this subgroup of Chinese patients may not be appropriate and may result in underdose.

Adolescent↗
PubMed1999

Receptor binding activities of Schefflera triterpenoids and oligosaccharides.

Roots and leaves of Schefflera bodinieri were studied for their activity in the central nervous system (CNS) by bioassay-guided isolation in conjunction with receptor binding assays. As demonstrated in preliminary screening, ethanol extracts of leaves and roots of S. bodinieri showed strong binding affinity to a number of CNS receptors. Chemical investigation of this plant species was then conducted and fourteen plant ingredients were obtained. In this study, nine of these isolated compounds were tested by fifteen receptor binding assays for their CNS activities. Results showed that three compounds, namely bodinone, bodinone glycoside and D-sorbitol, were able to selectively bind to muscarine receptors, a trisaccharide bound to Ca2+ channel and 5HT-2 receptors, stigmasterol 3-O-glucoside bound to 5HT-2 receptors, and bodirin A bound to dopamine-2 receptors with IC50 values at microM level. In the drug-interaction studies, bodinone, bodinone glycoside, bodirin A, bodinitin A and the trisaccharide were found to affect binding affinity of certain specific binding agents to the 5HT1C, 5HT2, opiate, beta-adrenergic and histamine 1 receptors. These observations suggest interactions between the plant ingredients and receptors as well as synergistic effect of various compounds at receptor level.

Animals↗
PubMed1999

Markedly different rates and resistance profiles exhibited by seven commonly used and newer beta-lactams on the selection of resistant variants of Enterobacter cloacae.

Seven beta-lactam antibiotics (cefepime, cefoperazone, ceftazidime, ceftriaxone, cefamandole, imipenem and meropenem) were tested for their potential to select resistance in standard and clinical strains of Enterobacter cloacae (n = 9). The strains were subcultured daily with the test antibiotics at doubling concentrations starting at 0.125 x MIC. Development of resistance throughout the passages was detected by a disc diffusion test. Ceftazidime, ceftriaxone and cefamandole selected resistance at a faster rate than cefoperazone, cefepime and meropenem. Imipenem did not select resistance in the nine strains tested and was the only antibiotic that eradicated all the strains during selection. The resistance patterns of strains selected by meropenem, cefepime and the other cephalosporins were markedly different, although cross-resistance to the early generation cephalosporins was common. The resistance phenotypes of most strains remained stable upon serial passages in antibiotic-free medium. The findings of this study highlight the importance of the choice of antibiotic for therapy not only on the basis of its antibacterial activity, but also on its potential to select resistance to itself and other antibiotics.

Anti-Bacterial Agents↗
PubMed1999

Influence of Sanguisorba officinalis, a mineral-rich plant drug, on the pharmacokinetics of ciprofloxacin in the rat.

The significance of an interaction between ciprofloxacin and Sanguisorba officinalis L. (SO), a mineral-rich herbal medicine, was evaluated in this study. Male Sprague-Dawley rats (220-250 g) receiving ciprofloxacin dosages of 20 mg/kg po were concomitantly dosed with an aqueous extract of SO (equivalent to 2 g/kg crude drug). Blood and urine samples were collected over 6 and 24 h, respectively, for the quantitation of ciprofloxacin by HPLC. The presence of SO reduced significantly (P < 0.05) the maximum plasma concentration, the area under the concentration-time curve and the urinary recovery of ciprofloxacin, by 94%, 78% and 79%, respectively, compared with rats receiving only ciprofloxacin. The presence of SO also caused an eight-fold and two-fold increase in drug distribution (Vd, lambda(z)/F) and terminal elimination half-life (t1/2, lambda(z)) from 30.8 L/kg and 1.96 h, respectively. Therefore, should the use of both agents be required, sufficient time should be allowed to ensure the efficacy of ciprofloxacin.

Animals↗
PubMed1999

PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits.

Using conscious rabbits, we examined the effect of ischemic preconditioning (PC) on p44 and p42 mitogen-activated protein kinases (MAPKs). We found that both isoforms contribute significantly to total MAPK activity in the heart (in-gel kinase assay: p44, 59 +/- 1%; p42, 41 +/- 1%). Ischemic PC (6 cycles of 4-min occlusion/4-min reperfusion) elicited a pronounced increase in total cellular MAPK activity (+89%). This increase, which occurred exclusively in the nuclear fraction, was contributed by both isoforms (in-gel kinase assay: p44, +97%; p42, +210%) and was accompanied by migration of the two proteins from the cytosolic to the nuclear compartment. In control rabbits, MAPK kinase (MEK)1 and MEK2, direct activators of p44 and p42 MAPKs, were located almost exclusively in the cytosolic fraction. Ischemic PC induced a marked increase in cytosolic MEK activity (+164%), whereas nuclear MEK activity did not change, indicating that MEK-induced activation of MAPKs occurred in the cytosolic compartment. Activation of MAPKs after ischemic PC was completely blocked by the protein kinase C (PKC) inhibitor chelerythrine. Selective overexpression of PKC-epsilon in adult rabbit cardiomyocytes induced activation of both p44 and p42 MAPKs and reduced lactate dehydrogenase release during simulated ischemia-reperfusion, which was abolished by the MEK inhibitor PD-98059. The results demonstrate that 1) ischemic PC induces a rapid activation of p44 and p42 MAPKs in hearts of conscious rabbits; 2) the mechanism of this phenomenon involves activation of p44 and p42 MAPKs in the cytosol and their subsequent translocation to the nucleus; and 3) it occurs via a PKC-mediated signaling pathway. The in vitro data implicate PKC-epsilon as the specific isoform responsible for PKC-induced MAPK activation and suggest that p44/p42 MAPKs contribute to PKC-epsilon-mediated protection against simulated ischemia. The results are compatible with the hypothesis that p44 and p42 MAPKs may play a role in myocardial adaptations to ischemic stress.

Alkaloids↗
PubMed1999

PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits.

A conscious rabbit model was used to study the effect of ischemic preconditioning (PC) on stress-activated kinases [c-Jun NH(2)-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK)] in an environment free of surgical trauma and attending external stress. Ischemic PC (6 cycles of 4-min ischemia/4-min reperfusion) induced significant activation of protein kinase C (PKC)-epsilon in the particulate fraction, which was associated with activation of p46 JNK in the nuclear fraction and p54 JNK in the cytosolic fraction; all of these changes were completely abolised by the PKC inhibitor chelerythrine. Selective enhancement of PKC-epsilon activity in adult rabbit cardiac myocytes resulted in enhanced activity of p46/p54 JNKs, providing direct in vitro evidence that PKC-epsilon is coupled to both kinases. Studies in rabbits showed that the activation of p46 JNK occurred during ischemia, whereas that of p54 JNK occurred after reperfusion. A single 4-min period of ischemia induced a robust activation of the p38 MAPK cascade, which, however, was attenuated after 5 min of reperfusion and disappeared after six cycles of 4-min ischemia/reperfusion. Overexpression of PKC-epsilon in cardiac myocytes failed to increase the p38 MAPK activity. These results demonstrate that ischemic PC activates p46 and p54 JNKs via a PKC-epsilon-dependent signaling pathway and that there are important differences between p46 and p54 JNKs with respect to the subcellular compartment (cytosolic vs. nuclear) and the mechanism (ischemia vs. reperfusion) of their activation after ischemic PC.

Alkaloids↗
PubMed1999

Effects of order of magnesium exposure on the postantibiotic effect and bactericidal activity of ciprofloxacin.

Quinolone antibiotics are known to form chelates with various metal cations. It has also been recognized that the physicochemical properties of the chelated antibiotic differ significantly from its unchelated form, thereby causing a reduction in antimicrobial activity. In addition, the formation of metal chelates is also believed to be the reason for the significant reduction in oral bioavailability for the quinolones when concomitantly dosed with oral cation containing agents. This has prompted the adoption of an alternate dosing regimen by introducing an adequate interval between the two. As a result of this dosing strategy, pathogens are exposed to the quinolones and metal cations in alternate orders. Using magnesium, ciprofloxacin, and Escherichia coli as the test organism, investigations were conducted to study the changes in bactericidal activity and postantibiotic effect (PAE) in relation to the orders of cation/antibiotic exposure. Results showed a parallel decrease in both bactericidal activity and PAE when the test organism was exposed to the two agents simultaneously; however, no apparent influences on these two antimicrobial effects were observed when Mg2+ was presented before or after ciprofloxacin exposure. In line with the current dosing recommendations, the interval spaced between ciprofloxacin and Mg2+ should preserve both the bactericidal activity and PAE exhibited by the antibiotic. How the present data are to be extrapolated to other quinolones and cations should be the subject of future studies.

Anti-Infective Agents↗
PubMed1999

Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats.

We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.

Animals↗
PubMed1999

Effect of oral administration of fennel (Foeniculum vulgare) on ciprofloxacin absorption and disposition in the rat.

The aim of this study was to investigate the possibility of a drug-drug interaction between ciprofloxacin and fennel (Foeniculum vulgare) in a rat model. Pharmacokinetic assessment of ciprofloxacin was performed in two groups of male Sprague-Dawley rats. One group (n = 5) received 20 mg kg(-1) antibiotic orally with concomitant oral dosing of the aqueous fennel extract (2 g herb kg(-1)) whereas the controls (n = 5) received 20 mg kg(-1) oral ciprofloxacin. Blood and urine samples were collected over 6 and 24 h, respectively, for quantitation of ciprofloxacin by HPLC. A non-compartmental model was employed for pharmacokinetic analysis. Major ingredients and metal cations in the fennel extract were determined. Compared with the control, maximum plasma concentration, area under the curve and urinary recovery of ciprofloxacin were significantly (P < 0.05) lower, by 83, 48 and 43%, respectively, in rats receiving concomitant dosing of the two agents. The relative bioavailability of ciprofloxacin, under the influence of fennel, was estimated to be 0.52. In addition, its apparent volume of distribution and terminal elimination half-life were significantly (P < 0.05) increased, from 30.8 +/- 11.1 (L kg(-1)) and 2.0 +/- 0.4 (h) to 143.8 +/- 31.6 (L kg(-1)) and 5.2 +/- 2.0 (h), respectively. Although none of the organic components of fennel seemed to cause this interaction, the total amount of ten metal cations measured was found to be 13 mg g(-1). Significant interaction between ciprofloxacin and fennel was observed in this study. Absorption, distribution and elimination of ciprofloxacin were all affected. These changes might be because of the formation of a more lipophilic ciprofloxacin chelate in the presence of relatively large amounts of metal cations. If, therefore, the two therapeutic agents are used concurrently, an adequate dosing interval is needed to ensure the efficacy of ciprofloxacin.

Administration, Oral↗
PubMed1999

Achieving an optimal outcome in the treatment of infections. The role of clinical pharmacokinetics and pharmacodynamics of antimicrobials.

Over the past few decades, the importance of applying pharmacokinetic principles to the design of drug regimens has been increasingly recognised by clinicians. From the perspective of antimicrobial chemotherapy, an improvement in clinical outcome and/or a reduction in toxicity are of primary interest. Before application of these pharmacokinetic theories can be effective, the interrelationships between antimicrobial, pathogen and host factors must be clearly defined. Information regarding the pharmacokinetics of the antimicrobial and the quantification of pathogen susceptibility is required. Even though susceptibility end-points such as minimum inhibitory concentration (MIC) and minimum bactericidal concentration are widely employed, they do not provide any information on dynamic changes of bacterial densities. In this regard, time-kill studies can provide more basic knowledge of the complex bacterial responses to the antimicrobial. Better prediction of these responses can be afforded by the use of mathematical models. More recently, various surrogate end-points employing a combination of suitable pharmacokinetic parameters and susceptibility data, for example the ratio of peak concentration to MIC, the area under the concentration-time curve above the MIC (AUC > MIC), the time above the MIC, or the area under the inhibitory curve (AUIC), have been suggested for better prediction of the activity of different classes of antimicrobials. To allow more extensive investigations of the contribution of pharmacokinetics to the pharmacodynamics of antimicrobials, various in vitro kinetic models have been developed. However, certain limitations exist, and it is necessary to avoid over-interpretation of the data generated by these models. Two important microbial dynamic responses, postantibiotic effect and resistance selection, must be further explored before the full impact of pharmacokinetics on antimicrobial chemotherapy can be depicted. The present paper aims at discussing all the relevant factors and provides some pertinent information on the use of pharmacokinetic-pharmacodynamic principles in antimicrobial therapy.

Animals↗
PubMed1998

Impact of pharmacokinetics on the postantibiotic effect exhibited by Pseudomonas aeruginosa following tobramycin exposure: application of an in-vitro model.

The postantibiotic effect (PAE) exhibited by Pseudomonas aeruginosa after exposure to single doses of tobramycin was investigated under various pharmacokinetic conditions using an established in-vitro kinetic model. At equal doses of the antibiotic stimulating an intravenous bolus condition, the effects of varying elimination half-life on PAE were assessed. The PAE was longer when the rate of antibiotic elimination was lower. However, after correcting for the different degrees of antibiotic exposure using the area under the concentration-time curve above the MIC (AUC > MIC), a coherent PAE versus antibiotic exposure profile was obtained. The effects of increasing tobramycin dose and exposure time on PAE were investigated in another series of experiments; PAE was assessed during antibiotic exposure when the exponentially decreasing concentrations were above the MIC, at the MIC and below the MIC. A longer PAE was achieved at higher doses and changes were dependent on both the degree and time of exposure. For all the doses tested, the PAE was longest when the decreasing antibiotic concentrations were near or at the MIC. Shorter PAEs were detected at sub-MIC concentrations and diminished rapidly as antibiotic concentrations continued to decline. Such a decrease in PAE was counteracted by the longer exposure time, so that the total time for which the organism was under the influence of the antimicrobial effects, i.e. the sum of exposure time and PAE, remained steady at sub-MIC concentrations. Under these simulated pharmacokinetic conditions, present data support a substantial impact of pharmacokinetics on PAE. Along with MIC, AUC > MIC can be a useful pharmacokinetic parameter for PAE assessments. Should PAE be a relevant factor in antibiotic chemotherapy, both time and degree of antibiotic exposure would have to be considered.

Anti-Bacterial Agents↗
PubMed1998

Parameterization of inoculum effect via mathematical modeling: aminoglycosides against Staphylococcus aureus and Escherichia coli.

Inoculum effect describes the inoculum size dependent changes in minimum inhibitory concentrations (MIC) exhibited by antibiotic-bacterium combinations demonstrating such effect. Traditionally, inoculum effect has been loosely defined based on the extent of increase in the MIC with respect to the increase in inoculum size. In most studies, assessment of MIC data has relied on the arbitrary selection of a point of reference for both baseline MIC and inoculum size. More importantly, this conventional method of assessment does not permit information conveyed in a complete MIC versus inoculum size profile to be fully explored. To undertake these issues, a mathematical model was developed for the description of the entire inoculum effect profile. With the employment of three key parameter estimates, i.e., the baseline MIC, the threshold inoculum size at which the increase in MIC commences, and the rate of increase in MIC with respect to inoculum size, both the shape and location of the profile could be adequately defined. To verify the application of this model, a series of four aminoglycosides were tested against standard strains of E. coli and S. aureus. Results showed a good degree of organism specificity and antibiotic-class dependency of the inoculum effect profiles. Analysis of the parameter estimates obtained provided further support for these observations. In conclusion, the mathematical model developed in the present study adequately described the inoculum effect exhibited by the various aminoglycoside-bacterium combinations tested. The parameter estimates generated by the modeling approach allowed comparison and quantitative analysis of the inoculum effect profiles with minimal difficulties.

Amikacin↗
PubMed1998

Assessment of presystemic factors on the oral bioavailability of rifampicin following multiple dosing.

This study was carried out to elucidate the possible mechanism(s) responsible for reduced oral rifampicin bioavailability after multiple dosing. In addition to autoinduction, the relative contribution of the two possible controlling factors, e.g., intestinal metabolism and microbial degradation, was investigated using a rat model. Pharmacokinetic studies were carried out to assess the absolute rifampicin bioavailability by both oral and intravenous drug administration before and after 8 daily doses of 25 mg/kg. To estimate the possible involvement of microbial degradation, rifampicin kinetics were also assessed in rats on day 8 after receiving multiple oral dosing and concurrent administration of nonabsorbable triple antibiotics for gut sterilization 3 days prior to the study day. Pharmacokinetic parameters were generated by noncompartmental analysis. The results revealed a significant decrease in rifampicin levels for rats after multiple exposure, compared to single dosing; the mean clearance determined by intravenous dosing increased by 43% from 3.7 ml/min/kg and the half-life decreased by 24% from 238 min. However, the extent of decrease in rifampicin exposure following multiple dosing was substantially greater for rats dosed orally than intravenously; estimated absolute oral bioavailability decreased by 15% from 0.89 on day 1 to 0.76 on day 8. No apparent alterations in any of the pharmacokinetic parameters were observed after gut sterilization, suggesting minimal contribution of microbial degradation to the reduction in oral rifampicin absorption after multiple dosing. In addition to hepatic enzyme autoinduction, these results strongly suggest the involvement of enhanced intestinal metabolism as a contributing factor to the decrease in oral rifampicin bioavailability following prolonged exposure.

Absorption↗
PubMed1997

Efficient high-performance liquid chromatographic assay for the simultaneous determination of metoprolol and two main metabolites in human urine by solid-phase extraction and fluorescence detection.

An improved, more efficient method for the determination of metoprolol and its two metabolites in human urine is reported. The simultaneous analysis of the zwitterionic metoprolol acidic metabolite (III, H117/04) with the basic metabolites alpha-hydroxymetoprolol (II, H119/66), metoprolol (I) and guanoxan (IV, internal standard) was achieved employing solid-phase extraction and isocratic reversed-phase HPLC. The analytes were extracted from urine (100 microliters) using C18 solid-phase extraction cartridges (100 mg), and eluted with aqueous acetic acid (0.1%, v/v)-methanol mixture (40:60, v/v, 1.2 ml). The eluents were concentrated (250 microliters) under vacuum, and aliquots (100 microliters) were analysed by HPLC with fluorescence detection at 229 nm (excitation) and 309 nm (emission) using simple isocratic reversed-phase HPLC (Novapak C18 radial compression cartridge, 4 microns, 100 x 5 mm I.D.). Acetonitrile-methanol-TEA/phosphate buffer pH 3.0 (9:1:90, v/v) was employed as the eluent (1.4 ml/min). All components were fully resolved within 18 min, and the calibration curves for the individual analytes were linear (r2 > or = 0.996) within the concentration range of 0.25-40.0 mg/ml. Recoveries for all four analytes were greater than 76% (n = 4). The assay method was validated with intra-day and inter-day variations less than 2.5%.

Administration, Oral↗