Copyright (c) 2010 All rights reserved. http://works.bepress.com/kelvin_chan Recent documents in Kelvin Chan en-us Fri, 19 Mar 2010 22:21:53 PDT 3600 http://works.bepress.com/kelvin_chan/116 http://works.bepress.com/kelvin_chan/116 Wed, 27 Aug 2008 23:30:23 PDT A sensitive and accurate gas liquid chromatographic (GLC) method is described to determine pethidine and norpethidine in plasma of Chinese patients who received a single dose (1 mg/kg of total body weight) of pethidine intramuscularly. The chromatograph consists of a 3% w/w SP2250 on Chromosorb W glass column linked to a nitrogen-phosphorus detector. Sample preparation was simple, being based on a single extraction of basified plasma samples with n-hexane. The operating time of the assay was less than thirty minutes, which was suitable for routine pharmacokinetic studies of both pethidine and norpethidine. This method was sensitive to 5 ng/ml of pethidine and 10 ng/ml of norpethidine extracted from 1 ml plasma sample. Linearity was observed in the range of 10 to 500 ng/ml. The day-to-day variation at the concentration of 100 ng/ml of pethidine and norpethidine was 3.3 and 4.27% respectively. The mean ( ± S.D.) peak plasma concentration, the mean ( ± S.D.) time for maximum absorption, and the mean ( ± S.D.) elimination half-life of pethidine was 246.4 ± 65.9 ng/ml, 0.75 ± 0.31 hr., and 7.95 ± 2.22 hrs respectively. The N-demethylated metabolite, norpethidine, appeared in the plasma from 0.5 to 1 hour and the mean ( ± S.D.) peak plasma concentration was 28.8 ± 4.38 ng/ml. The mean elimination half-life (39.6 ± 19.3 hrs) was significantly greater than pethidine. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/115 http://works.bepress.com/kelvin_chan/115 Wed, 27 Aug 2008 23:21:12 PDT We measured pyrazinamide and rifampicin plasma concentrations in five patients with pulmonary tuberculosis and end stage renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis. Using conventional daily doses of oral pyrazinamide and rifampicin, we found that the drugs were removed efficiently by both dialysis methods, so that plasma levels were sub-optimal for maximal bactericidal action. These findings suggest that in patients with tuberculosis on maintenance dialysis, treatment should be either with higher doses of these two drugs, or with additional replacement doses given after each dialysis. Further detailed pharmacokinetic studies on larger numbers of patients are indicated. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/114 http://works.bepress.com/kelvin_chan/114 Wed, 27 Aug 2008 23:15:19 PDT The present study aims to investigate the preclinical intestinal absorption of bis(7)-tacrine (B7T) using different absorption models. In addition, potential intestinal and liver first-pass metabolism was evaluated by in vitro incubation of B7T with rat intestine and liver microsome. Results showed that the permeability of B7T across artificial membrane was pH dependent with rapid diffusion achieved at both pH 6.8 and 7.4. However, the absorptive permeability of B7T in Caco-2 cell model was substantially lower than that in the artificial membrane accompanied with over 56% of B7T being trapped within Caco-2 cells. In the rat in situ intestinal perfusion model, B7T was subject to an extensive intestinal extraction (>90%) with extremely low concentration of B7T detected in mesenteric blood, which was further found to be associated with the high tissue binding (99.9%) of B7T. In vitro incubation of B7T with rat liver and intestinal microsomes revealed that hydroxylation of B7T might mainly occur in rat liver rather than intestine. In conclusion, B7T is expected to have a low oral bioavailability in vivo, which may be due to its poor intestinal permeability, significant tissue binding and hepatic hydroxylation metabolism. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/113 http://works.bepress.com/kelvin_chan/113 Wed, 27 Aug 2008 23:08:38 PDT The method involves a single extraction of the drug and the internal standard, etidocaine, from alkalinized plasma with n-hexane. The gas chromatograph is equipped with a glass column (2.0 m x 2 mm) packed with 3% W/W SP2250 on Chromosorb W, (80/100 mesh) and a nitrogen sensitive detector. The method can accurately measure plasma bupivacaine concentrations down to 0.01 µg ml-1 using a sample size of 0.5 ml. The day-to-day variation of bupivacaine at 2.0 µg ml-1 is 6.90% (n = 10). The calibration graph is linear over the range 0.1 - 4.0 µg ml-1. The method is accurate, fast and sensitive and has been applied in a pharmacokinetic study of bupivacaine. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/112 http://works.bepress.com/kelvin_chan/112 Wed, 27 Aug 2008 22:53:37 PDT We here provide definitive evidence that ginsenoside- Rg1, the pharmacologically active component of ginseng, is a functional ligand of the glucocorticoid receptor (GR) as determined by fluorescence polarization assay. Rg1 increased the phosphorylation of GR, phosphatidylinositol-3 kinase (PI3K), Akt/PKB and endothelial nitric oxide synthase (eNOS) leading to increase nitric oxide (NO) production in human umbilical vein endothelial cell. Rg1-induced eNOS phosphorylation and NO production were significantly reduced by RU486, LY294,002, or SH-6. Also, knockdown of GR completely eliminated the Rg1-induced NO production. This study revealed that Rgl can indeed serve as an agonist ligand for GR and the activated GR can induce rapid NO production from eNOS via the non-transcriptional PI3K/Akt pathway. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/111 http://works.bepress.com/kelvin_chan/111 Wed, 27 Aug 2008 22:47:13 PDT The urinary clearance of pyridostigmine was studied in six patients with myasthenia gravis. In three patients on pyridostigmine, alone, renal clearance ranged from 349 to 481 ml/min, corresponding to a pyridostigmine:creatinine clearance ratio of 2.64 to 3.46. In a patient on bendrofluazide as well as pyridostigmine, a similar clearance ratio was observed. By contrast, the urinary clearance of pyridostigmine and the pyridostigmine:creatinine clearance ratio was reduced in two myasthenic patients concurrently treated with other basic drugs. It is suggested that these results may reflect competition for renal tubular excretion. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/110 http://works.bepress.com/kelvin_chan/110 Wed, 27 Aug 2008 22:42:49 PDT The pharmacokinetics of pyrazinamide (PZA) in cerebrospinal fluid (CSF) and plasma of 10 rabbits were studied after separate intravenous (i.v.) and oral (p.o.) administration, in a cross-over study. Concentrations of PZA in biological fluids were determined by high-performance liquid chromatography (HPLC). After p.o. dose PZA was absorbed rapidly and peak plasma concentration was attained at 0.5 h post administration. After i.v. dose, the plasma PZA concentrations declined rapidly within 10 min and subsequently more slowly following a bi-exponential manner. No difference was observed int he area under plasma concentration-time curves indicating oral absorption was complete and no apparent first-pass metabolism occured. The (mean ± S.D.) elimination t1/2 after i.v. (1.04 ± 0.18 h) was significantly shorter (p = 0.0005) than that after oral (1.95 ± 0.63 h) dose and the apparent volume of distribution was also significantly smaller (P = 0.005) after i.v. (3.211 ± 0.412 l) than after oral (5.936 ± 1.607 l) administration. The elimination t1/2 of PZA in CSF was nearly identical to that in plasma after either i.v. (1.07 ± 0.20 h) or p.o. (1.84 ± 0.56 h) administration. There is no apparent barrier in rabbits for the penetration of PZA into CSF from the general circulation. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/109 http://works.bepress.com/kelvin_chan/109 Wed, 27 Aug 2008 22:34:17 PDT 219 surgical patients of either Caucasian, Chinese or Nepalese origin were given pethidine 1 mg/kg by intramuscular injection as pre-operative medication. Urine was collected for 24 h and analysed for pethidine, pethidinic acid, pethidinic scid conjugates, norpethidine, norpethidinic acid, and norpethidinic acid conjugates. The mean proportion of thc percentage of metabolites attributable to oxidative demethylation, hydrolysis and conjugation was almost identical in each ethnic gtoup (P > 0.2). It was concluded that there were no differences in the metabolic variability of the biotransformation of pethidine in Asians and Caucasians in whom the urine pH had not been acidified. Kelvin Chan http://works.bepress.com/kelvin_chan/108 http://works.bepress.com/kelvin_chan/108 Wed, 27 Aug 2008 22:27:14 PDT p-Aminobenzoic acid (PABA), p-acetamidobenzoic acid (PADB) and p-aminohippuric acid (PAH) have been separated and determined by a reversed phase, isocratic high performance liquid chromatographic (HPLC) procedure simultaneously. The mobile phase, at 1.5 ml min-1, used was 10 mM sodium hydrogen phosphate buffer, pH 3.5, containing 40% methanol. The eluent was detected at 270 nm. Linear relationship was obtained from 0 to 2.0 µg ml-1 of each compound with the corresponding peak-height ratio using p-methylamino-benzoic acid (PMAB) as the internal standard. Urine samples were obtained from healthy Chinese volunteers after oral dosing of 200 mg PABA which was used as a model substance for metabolic investigation of N-acetylation and other conjugation reactions. The 24 hour urinary recovery, from 43 healthy subjects, of PABA, PABA-COOH conjugates, PADB and PADB-COOH conjugates were (mean ± S.D.) 2.9 ± 1.5%, 5.2 ± 3.3%, 13.9 ± 4% and 42.9 ± 9.8% of the ingested dose respectively. These accounted for 64.9 ± 12.0% of total dose ingested in 24 hour. In contrast to previously reported findings on one Caucasian subject, no PAH was identified in the urine, and N-acetylation was the major route of metabolism of PABA apart from conjugation at the - COOH group in this group of Chinese volunteers. It is proposed that PABA metabolism may be a useful probe to study ethnic and geographic variation in N-acetylation. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/107 http://works.bepress.com/kelvin_chan/107 Wed, 27 Aug 2008 22:16:03 PDT The concentration-time profiles of ethmozine, a newly introduced anti-arrhythmic drug, in the cerebrospinal fluid (CSF) and plasma of six rabbits (New zealand white rabbits of both sexes, 4.0-5.0 kg) were studied after intravenous bolus administration. CSF samples at various intervals were obtained while the animal was lightly anaesthetized with intravenous thiopentone (40 mg Kg-1) and blood samples at other intervals were taken while the animal was conscious. Blood samples (1 ml) were collected from the implanted cannula of the ear artery while CSF samples (0.3 ml) were obtained from the cisterna magna. The plasma concentrations of ethmozine in six rabbits declined rapidly after intravenous injection for up to 30 min then slowly over 12 h. Using non-compartmental analysis, the mean (± S.E.M.) elimination half-life, mean residence time, plasma clearance and volume of distribution at steady state were 13.9 ± 9.2h, 19.9 ± 13.4 h, 2.3 Lh-1 and 26.8 ± 7.9 L respectively. The mean CSF-plasma concentration ratios for ethmozine at 0.5, 1.0, 2.0, 4.0, 8.0 and 12.0 h were 0.17, 0.14, 0.16, 0.16, 0.23 and 0.22 respectively. The results suggest that ethmozine is able to penetrate into the CSF from the general circulation and this maybe related to its adverse effects on the central nervous system. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/106 http://works.bepress.com/kelvin_chan/106 Wed, 27 Aug 2008 22:02:16 PDT Danshen is a Chinese folk medicine commonly used in the Chinese population. The effects of Danshen on the pharmacokinetics and pharmacodynamics of warfarin were studied in rats. In the phamacokinetic study, single oral doses of warfarin were administered to rats or after 3 days treatment with Danshen intraperitoneally twice daily. Plasma warfarin concentrations were measured for 48 h after each of two warfarin doses by high performance liquid chromatography (HPLC). In the pharmacodynamic study, the treatments were similar to the pharmacokinetic study, the prothrombin time (PT) was measured daily both in the Danshen treatment period and after the warfarin doses for 4 days. The absorption rate (Ka), volume of distribution (Vd) and elimination half-life (T1/2) of warfarin were significantly decreased while Cmax and Tmax were significantly increased affer treatment with Danshen. There was no significant change in PT during the Danshen treatment period while the PTs were increased significantly in the first two days after warfarin doses. Our results suggested that Danshen can increase the initial bioavailability of warfarin and also affect the elimination of warfarin. It can also increase the PT further after the warfarin doses. The pharmacokinetic and pharmacodynamic interactions observed in this study indicate a clinically important interaction between Danshen and warfarin if these two agents are taken together. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/105 http://works.bepress.com/kelvin_chan/105 Wed, 27 Aug 2008 21:48:49 PDT The present study reports findings on the disposition of epirubicin after an intrahepato-arterial administration of the Lipiodol-drug complex, prepared by mixing the drug-aqueous phase with the iodized oil by ultra-sonification, in 14 patients with histologically proven hepatoma or hepatomegaly with serum α-fetoprotein level above 500 µg.1-1. The volume of Lipiodol used was 5 ml and the epirubicin dose was 50mg.g-2. Blood samples were obstained at various time intervals up to 72 h post-dose. Serum concentrations of epirubicin were measured by liquid chromatography with fluorometric detection. The area under serum concentration-time curve (AUC) was higher in the Lipiodol-epirubicin group (n = 8) while the clearance was fater and elimination t1/2 and mean residence time shorter in the plain epirubicin group (n = 3). However, interindividual variation in metabolism of epirubicin would affect serum level of the drug. In three patients who were given intravenous and intrahepato-arterial injections (90 mg.m-2) or plain epirubicin and Lipiodol-drug complex, the relative bioavailability of Lipiodol-epirubicin complex (F = 0.76 and 0.45) was lower than that of plain epirubicin (F = 0.80 and 0.73) in two patients while it was approximately 100% (F = 1.06 and 1.20) in one patient. It is likely that liver function of the patients might be modified by the disease state over a period of 3 months in the cross-over study. Further studies with larger patient samples are required to confirm if there is a targeting effect of the Lipiodol-drug complex toward hepatoma using a better formulation of the drug in Lipiodol. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/104 http://works.bepress.com/kelvin_chan/104 Wed, 27 Aug 2008 04:00:31 PDT Danggui is a popular traditional Chinese medicinal (TCM) herb which is easily obtained by the public. The effects of Danggui on the pharmacokinetics and pharmacodynamics of warfarin were studied in rabbits. Single subcutaneous doses (2 mg/kg) of warfarin were administered to 6 rabbits with or without 3 days treatment with oral Danggui extracts (2 g/kg twice daily). Plasma warfarin concentrations were measured by high performance liquid chromatography (HPLC) for 72 h after each of the two warfarin doses. The prothrombin time (PT) was measured daily for 3 days both during the Danggui treatment period and after warfarin doses. Danggui treatment did not affect PT on its own, but significantly lowered PT values 3 days after co-treatment with single dose warfarin. No significant variations in the single dose pharmacokinetic parameters of warfarin were observed after Danggui treatment. A separiate group of 6 rabbits were given daily subcutaneous doses of warfarin (0.6 mg/kg) to achieve steady state level, followed by 3 day treatment with oral Danggui extract (2 g/kg twice daily). The slight increase in PT was not significant and two rabbits died after day 7 of the treatment period. However, there was no significant difference in steady state concentrations of warfarin after the Danggui treatment. Results indicate that precautionary advice should be given to patients who self medicate with Danggui or other TCM products while on chronic treatment with warfarin. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/103 http://works.bepress.com/kelvin_chan/103 Wed, 27 Aug 2008 03:19:41 PDT In a residential Symposium on "Peptides as Targets for Drug Research" at Vanbrugh College, University of York, U.K. organized by the Society of Drug Research, several experts from academia and pharmaceutical industries presented concepts, reviews and possible applications on various aspects of peptides which may be important in the development of new targets for drug research. The following is a summary of some salient points in this rapidly growing field, with general references for readers' further pursuits. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/102 http://works.bepress.com/kelvin_chan/102 Wed, 27 Aug 2008 03:16:33 PDT One of the highlights of the scientific program of the 1st Scientific Meeting of the Hong Kong Pharmacology Society (HKPS), held on December 15th and 16th, 1987, was that of the Symposium on Modern Antimalarial Drug Therapy. Well-known researchers in this field from Southeast Asia and China were inivited speakers at the symposium. A concise overview of this symposium is given here. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/101 http://works.bepress.com/kelvin_chan/101 Wed, 27 Aug 2008 03:10:44 PDT Using a high performance liquid chromatography assay, pyrazinamide and rifampicin concentrations were measured in paired samples of cerebrospinal fluid (CSF) and serum obtained 2, 5, and 8 hours after oral drug administration in 12 patients with tuberculous meningitis. Penetration of pyrazinamide into CSF was good, with the CSF concentration exceeding that of serum by five to eight hours. The maximum CSF concentration achieved was mcre than twice the minimum inhibitory concentration (MIC) for 85% of local strains of Mycobacterium tuberculosis. Penetration appeared greater at five hours in the earlier stages of the disease. By contrast, penetration of rifampicin was comparatively poor, the maximum concentration reached in the CSF being only one tenth that of serum at eight hours. Moreover, the level did not reach MICs for 20% of local strains of M tuberculosis. Penetration appeared to be proportional to the extent of meningeal inflammation as assessed by CSF protein concentration and white cell count. Use of steroids did not appear to influence either pyrazinamide or rifampicin penetration into the CSF. It is concluded that with the present oral dosages of pyrazinamide (31 to 33 mg/kg), adequate CSF levels are reached. However, for rifampicin, (mean dose, 11 to 12 mg/kg), the CSF concentration may not reach the MIC in a proportion of patients, so that further studies are needed to determine optimum dosage and method of drug administration in order to achieve therapeutic CSF levels. Kelvin Chan Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/100 http://works.bepress.com/kelvin_chan/100 Wed, 27 Aug 2008 03:01:40 PDT Activity of Chinese Danggui (DG), the processed root of Angelica sinensis (Oliv.) Diels, is linked to the ferulic acid content but the stability of ferulic acid during extraction for medicinal use is not known. The stabilities of ferulic acid and coniferyl acid were evaluated in the extracts of DG using a variety of extraction solvents. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/99 http://works.bepress.com/kelvin_chan/99 Wed, 27 Aug 2008 02:59:02 PDT Background: This paper describes the development of the Chinese Quality of Life Instrument (ChQOL) which is a self-report health status instrument. Chinese Medicine relies very much on asking subjective feelings of patients in the process of diagnosis and monitoring of treatment. For thousands of years, Chinese Medicine practitioners have accumulated a good wealth of experiences in asking questions about health of their patients based on the concept of health in Chinese Medicine. These experiences were then transformed into questions for the ChQOL. It is believed that ChQOL can contribute to the existing Patient Report Outcome measures. This paper outlines the concept of health and disease in Traditional Chinese Medicine, the building of the conceptual framework of the ChQOL, the steps of drafting, selecting and validating the items, and the psychometric properties of the ChQOL. Methods: The development of the ChQOL was based on the concept of health in Traditional Chinese Medicine with a theory driven approach. Based on the results of literature review, the research team developed an initial model of health which encompassed the concept of health in TCM. An expert panel was then invited to comment and give suggestions for improvement of the initial model. According to their suggestions, the model was refined and a set of initial items for the ChQOL was drafted. The refined model, together with the key domains, facets and initial items of the ChQOL were then mailed to a sample of about 100 Chinese medicine practitioners throughout Mainland China for their comments and advice. A revised set of items were developed for linguistic testing by a convenience sample consisting of both healthy people and people who attended Chinese Medicine treatment. After that, an item pool was developed for field-testing. Field test was conducted on a convenience sample of healthy and patient subjects to determine the construct validity and psychometric properties of the ChQOL. Results: Construct validity was established by various methods, i.e. the internal consistency in all facets and domains were good; the correlation between facets to domain, and domains to overallChQOL correlation were high; confirmatory factor analysis showed that the structure fitness of all facets, domain and overall structure were good with CFI > 0.9. Test-retest reliability was also good, especially in the domain scores with ICC value ranging from 0.83 to 0.90. No ceiling or floor effect was noted which indicated that ChQOL can be applied to subjects with a wide range of health status. Most facet scores, domain scores and the overall CHQOL scores were able to discriminate groups of subjects with known differences in health status. The ChQOL had mild positive convergence with the other generic health related QOL measures, i.e. the WHOQOL-100 and the SF-36, with moderate correlations. Conclusion: In conclusion, the study indicated that the ChQOL is conceptually valid with satisfactory psychometric properties. It can provide additional information on health and QOL on top of the existing generic health related QOL measures. Furthermore, it forms basis for further testing and applications in clinical trials. Kelvin Chan Chinese Medicine http://works.bepress.com/kelvin_chan/98 http://works.bepress.com/kelvin_chan/98 Wed, 27 Aug 2008 02:57:22 PDT The major active constituents of ginseng are ginsenosides, and Rg1 is a predominant compound of the total extract. Recent studies have demonstrated that Rg1 can promote angiogenesis in vivo and in vitro. In this study, we used a DNA microarray technology to elucidate the mechanisms of action of Rg1. We report that Rg1 induces the proliferation of HUVECs, monitored using [3H]-thymidine incorporation and Trypan blue exclusion assays. Furthermore, Rg1 (150-600 nM) also showed an enhanced tube forming inducing effect on the HUVEC. Rg1 was also demonstrated to promote angiogenesis in an in vivo Matrigel plug assay, and increase endothelial sprouting in the ex vivo rat aorta ring assay. Differential gene expression profile of HUVEC following treatment with Rg1 revealed the expression of genes related to cell adhesion, migration and cytoskeleton, including RhoA, RhoB, IQGAP1, CALM2, Vav2 and LAMA4. Our results suggest that Rg1 can promote angiogenesis in multiple models, and this effect is partly due to the modulation of genes that are involved in the cytoskeletal dynamics, cell-cell adhesion and migration. Kelvin Chan Chinese Medicine Pharmacokinetics, Biochemistry http://works.bepress.com/kelvin_chan/97 http://works.bepress.com/kelvin_chan/97 Wed, 27 Aug 2008 02:55:10 PDT Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to treat rheumatoid arthritis. While, in theory, either herb could be used alone, in practice, Chinese medicine practitioners prescribe them together. Studies on pharmacokinetic interaction between the active constituents of these two herbs (paeoniflorin and sinomenine, respectively) provide empirical evidence to support their clinical practice.Asingle dose of paeoniflorin (150 mg/kg) alone and with sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to unrestrained conscious male Sprague-Dawley rats (n=6, 250-300 g). Blood samples were collected periodically via a jugular vein before and after dosing from 10 min to 12 h.Ahigh-performance liquid chromatographic (HPLC) assay was developed to determine the plasma concentrations of paeoniflorin. Non-compartmental pharmacokinetic profiles were constructed by using the software PK Solutions 2.0. The pharmacokinetic parameters were compared using unpaired Student t-test. After co-administration of sinomenine, the peak plasma concentration of paeoniflorin was elevated (P < 0.01), the peak time was delayed (P < 0.01), the AUC0-t was increased (P < 0.001), the mean residence time (MRT) was prolonged (P < 0.01), the CL was decreased (P < 0.01) and the Vd was reduced (P < 0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg significantly improved the bioavailability of paeoniflorin in rats. Kelvin Chan Pharmacokinetics, Biochemistry