Biomedical subjects

Suk-Jae Chung

Publications and source records attributed to Suk-Jae Chung.

At least 19 recordsLinked to original sources

PubMed2007

Air-liquid interface (ALI) culture of human bronchial epithelial cell monolayers as an in vitro model for airway drug transport studies.

Serially passaged normal human bronchial epithelial (NHBE) cell monolayers were established on Transwell inserts via an air-liquid interface (ALI) culture method. NHBE cells were seeded on polyester Transwell inserts, followed by an ALI culture from day 3, which resulted in peak TEER value of 766+/-154 Omegaxcm2 on the 8th day. Morphological characteristics were observed by light microscopy and SEM, while the formation of tight junctions was visualized by actin staining, and confirmed successful formation of a tight monolayer. The transepithelial permeability (Papp) of model drugs significantly increased with the increase of lipophilicity and showed a good linear relationship, which indicated that lipophilicity is an important factor in determining the Papp value. The expression of P-gp transporter in NHBE cell monolayers was confirmed by the significantly higher basolateral to apical permeability of rhodamine123 than that of reverse direction and RT-PCR of MDR1 mRNA. However, the symmetric transport of fexofenadine.HCl in this NHBE cell monolayers study seems to be due to the low expression of P-gp transporter and/or to its saturation with high concentration of fexofenadine.HCl. Thus, the development of tight junction and the expression of P-gp in the NHBE cell monolayers in this study imply that they could be a suitable in vitro model for evaluation of systemic drug absorption via airway delivery, and that they reflect in vivo condition better than P-gp over-expressed cell line models.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Enhancing effect of surfactants on fexofenadine.HCl transport across the human nasal epithelial cell monolayer.

The effect of various surfactants (sodium cholate, sodium taurocholate, Tween 80 and Poloxamer F68) on enhancing the transepithelial permeability of fexofenadine.HCl was evaluated in a human nasal epithelial cell monolayer model. The cytotoxicity of the surfactants on the human nasal epithelial cells was evaluated by the MTT assay. A dose-dependent reduction of cell viability was observed at higher than critical micelle concentration (CMC) of the surfactants, and the IC50 of non-ionic surfactants (Tween 80 and Poloxamer F68) was higher than that of ionic surfactants (sodium cholate and sodium taurocholate). The TEER values significantly decreased after 2 h incubation with the ionic surfactants, but were recovered after 24 h in the fresh culture media. Ionic surfactants significantly increased the transepithelial permeability (P(app)) of fexofenadine.HCl compared to the non-ionic surfactants. The reduction of TEER values upon exposing the cell monolayer to the surfactants for 2 h correlated well with the P(app) of fexofenadine.HCl, which suggests that the permeation-enhancing mechanism of the ionic surfactants is by altering the tight junction property of the paracellular pathway. F-actin staining showed that the effect of ionic surfactants on the tight junction is temporary and reversible, which is consistent with the TEER value recovery within 24 h. These results imply that ionic surfactants are potentially useful permeation enhancers for nasal delivery of hydrophilic compounds, such as fexofenadine.HCl. This study also indicated the usefulness of the human nasal epithelial cell monolayer model not only for evaluating the in vitro nasal drug transport but also for studying the mechanism and toxicity of enhancers.

Cell Membrane Permeability↗

PubMed2006

Quantification of clotiazepam in human plasma by gas chromatography-mass spectrometry.

An analytical procedure was developed and validated for the quantification of clotiazepam in human plasma. After subjecting plasma samples to solid-phase extraction, the extract was evaporated and the residue re-constituted. An aliquot of the mixture was injected onto a gas chromatography-mass spectrometry system. The detector response was linear for clotiazepam concentrations in the range of 5-200 ng/ml. Intra- and inter-day precision for the assay over the concentration range was below 13.1 and 13.5%, and the accuracy ranged between 99.0-107.9% and 92.4-101.3%, respectively. The drug was found to be stable under various processing conditions used. The method is applicable to human pharmacokinetic studies of clotiazepam.

Azepines↗

PubMed2006

Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer.

PURPOSE: Oxaliplatin and 5-fluorouracil (5-FU) act synergistically in colorectal cancer. Here, we evaluated the pharmacokinetics of oxaliplatin and 5-FU administered in combination with leucovorin in Korean advanced colorectal cancer patients. METHODS: Nine patients with advanced colorectal cancer were included in this study. The 3-week regimen consisted of oxaliplatin (2-h infusion, 130 mg/m(2)on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m(2), respectively, from day 1 to day 5). Blood samples were taken and platinum concentrations in total plasma, plasma ultrafiltrate, and RBCs were determined. Plasma concentrations of 5-FU were also determined. RESULTS: The C (max) of oxaliplatin was observed at the end of infusion, with mean values of 4.66, 0.84, and 2.69 microg/ml for total plasma, plasma ultrafiltrate, and RBC samples, respectively. C (max) ratios of total/free were significantly higher than those reported in other ethnic groups. An accumulation of platinum was observed in RBCs, but not in total plasma and plasma ultrafiltrate samples. A significant correlation was found between the total body clearance of ultrafiltrable platinum and creatinine clearance. The C (max) of plasma 5-FU ranged from 23.9 to 533.8 ng/ml, indicating large inter-patient pharmacokinetic variations. CONCLUSIONS: This study shows that pharmacokinetics of oxaliplatin in Korean patients is comparable with that of other ethic groups, except for the higher C (max) ratios of total/free. The C (max) of 5-FU in plasma showed large variations among patients. Antitumor efficacy in Korean advanced colorectal cancer patients given oxaliplatin and 5-FU should be further evaluated with respect to pharmacokinetic variabilities.

Adenocarcinoma↗

PubMed2006

Mechanism for increased bioavailability of tacrine in fasted rats.

The mechanism associated with the increased bioavailability of tacrine as a result of a 24-h period of fasting was examined in rats. The AUC value for tacrine after the fasting was 52% higher compared with normal feeding when 4 mg kg(-1) of tacrine was orally administered, but the value for velnacrine, a hydroxylated metabolite of tacrine, was reduced by 10%. The relative metabolic ratio of tacrine in urinary excretion (Au(tacrine) divided by Au(velnacrine)) was lower in fasted rats compared with normally fed rats. This clearly shows that metabolism of tacrine is reduced with 24-h fasting after oral administration. Altered intestinal permeation in the fasting state was hypothesized, and the transport of tacrine across the rat intestine was studied. When a fasted intestine was mounted in an Ussing chamber, the mucosal-to-serosal permeability of tacrine was increased to double that for a fed rat intestine. To examine the effect of absorption rate on the hepatic metabolism of tacrine, a direct pyloric vein infusion study was carried out. Compared with an infusion of tacrine for 5 min, a slow infusion of tacrine over a period of 30 or 60 min increased the hepatic metabolism of tacrine and decreased its systemic clearance in rats. Collectively, these results suggest that rapid transport across the intestine aids tacrine in avoiding hepatic first-pass metabolism and enhances its bioavailability in fasted rats. From these findings, we conclude that both oral administration before a meal and a reduction in the dose might be recommended in tacrine therapy considering the serious hepatotoxicity of tacrine in clinical use.

Administration, Oral↗

PubMed2006

Application of a sample pooling method for the accelerated assessment of the rate of uptake of drugs by the brain in rats.

The purpose of this study was to examine the feasibility of applying a sample pooling method to the accelerated estimation of the uptake clearance of drugs to the brain in rats. Brain uptake clearances (CL(uptake)) were estimated for five model compounds using the sample pooling method and an integration plot analysis. CL(uptake) was also evaluated for caffeine and theophylline by brain microdialysis. The parameters and throughput of the pooling method were compared with those of typically used standard methods. The correlation for CL(uptake) was statistically significant (P<0.005) between the integration plot and the current method; the throughput of evaluation was 15-fold higher for the sample pooling method. A comparison of CL(uptake) values indicated that the three methods showed comparable results for caffeine while the CL(uptake) of theophylline using the proposed method was significantly different from those of the other methods. A kinetic analysis indicated that a compound with a slower CL(uptake) and longer half-life (e.g., theophylline) is more prone to error and that the lower limit of the CL(uptake) of 0.17 mL min(-1) (g brain)(-1) may be set so as to have an error less than 20% of the estimation. These results suggest that the sample pooling method is applicable for use in the accelerated estimation of the uptake clearance of compounds in the brain for which the value is greater than 0.17 mL min(-1) (g brain)(-1).

Animals↗

PubMed2005

Effect of nonylphenol ethoxylates (NPEs) on barrier functions of epithelial cell membranes: opening of tight junctions and competitive inhibition of P-gp-mediated efflux.

The effect of nonylphenol ethoxylates (NPEs) on selected barrier functions of biological membranes, such as tight junction and P-gp efflux pump of epithelial membranes, against the transport of xenobiotics was examined. The Caco-2 cell line was used to evaluate the transport of mannitol and daunomycin across the cell monolayer as well as the cellular uptake of daunomycin. In the presence of NPEs, the transport of mannitol was increased, with NP-9 showing a maximal effect, and the transepithelial electrical resistance (TEER) was reduced. The onset of this effect of NP-9 was fairly rapid and reversible for a short term (e.g., 2 h) treatment, while irreversible for a long term (e.g., 72 h) treatment. In the presence of NP-9, the apical uptake of daunomycin was increased, suggesting competitive inhibition between NP-9 and daunomycin in the efflux via the P-gp system. However, a 72 h pretreatment of the cells with NP-9 (up to 1000 nM) did not affect the apparent cellular uptake of daunomycin, suggesting no significant effect of NPEs on the expression of P-gp. In conclusion, NPEs appear to rapidly open the tight junction of epithelial cell membranes and to competitively inhibit the efflux of P-gp substrates, thereby reducing the self-protection ability of the organism against xenobiotics or hazardous environmental compounds that are transported via the paracellular pathway (i.e., uptake) or the P-gp system (i.e., efflux).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Prokinetic activity of an aqueous extract from dried immature fruit of Poncirus trifoliata (L.) Raf.

Aqueous extracts from dried immature fruit of Poncirus trifoliata Raf. (Rutaceae) (PF-W) are used as a traditional Korean folk medicine for the treatment of digestive dysfunction. In the present study, PF-W exhibited no significant toxicity even at a dose of 5 g/kg when orally administered to mice. The effect of PF-W on gastrointestinal (GI) motor function was investigated by examining its effect on the serum concentration of orally administered ranitidine, a putative indicator of GI motility, in human subjects. The area under the serum concentration-time curve and the peak serum concentration of ranitidine following an oral administration (300 mg/individual) were decreased by one half as the result of a predose (10 g/individual) of PF-W, except for the time to reach peak serum concentration and the serum half-life at the terminal phase of ranitidine. In rat studies, PF-W had no effect on the apparent permeability of ranitidine across the jejunum or the gastric emptying rate (GER) of phenol red. However, the transit time for charcoal in the intestine was significantly increased by the PF-W pretreatment. The above results are consistent with the hypothesis that PF-W has a unique prokinetic activity, which accelerates the transit of intestinal contents, but has no effect on the GER.

Animals↗

PubMed2005

Effect of an aqueous extract of dried immature fruit of Poncirus trifoliata (L.) Raf. on intestinal transit in rodents with experimental gastrointestinal motility dysfunctions.

The effect of an aqueous extract of the dried immature fruit of Poncirus trifoliata Raf. (Rutaceae) (PF-W) on gastrointestinal (GI) motor function was investigated by measuring the intestinal transit rate (ITR) of Evans blue in rats and mice with experimental GI motility dysfunctions (GMDs). GMD was induced by appropriate surgery or by the administration of acetic acid, atropine, L-DOPA, or morphine to the animals. The ITR in these GMD animals was significantly retarded compared to normal animals. The retardation, however, was significantly inhibited by the intragastric administration of PF-W (0.1-1g/kg) in a dose dependent manner for all GMD models except for L-DOPA-induced GMD. The above results suggest that PF-W has the potential for development as a prokinetic agent that may prevent or alleviate GMD in human patients.

Animals↗

PubMed2005

Enhanced intestinal absorption of salmon calcitonin (sCT) from proliposomes containing bile salts.

PURPOSE: The feasibility of using proliposomes containing salmon calcitonin (sCT) and absorption enhancing agents, as an oral delivery system, to improve the intestinal absorption of sCT was explored using rats and Caco-2 cell systems. METHODS: Seventeen surfactants were examined for their effects with reference to accelerating the permeability of sCT (300 microg/ml) across Caco-2 cell monolayers, and damage to the intestinal epithelial cells, as measured by the change in transepithelial electrical resistance (TEER) across the cell monolayer. Proliposomes containing sCT (0.75%, w/w) and sodium taurodeoxycholate (NaTDC, 2.5%, w/w) (TDC proliposomes) were prepared according to the standard method using sorbitol and phosphatidylcholine as core and wall-forming materials, respectively, administered intra-duodenally to rats, and plasma concentrations of sCT were subsequently determined by LC-MS. RESULTS: Among the surfactants examined, some bile salts including NaTDC appeared to be the most advantageous when estimated based on the balance between the permeation enhancement (e.g., a 10.8-fold increase in the permeability of sCT for 0.1% NaTDC) and damage to the cells (e.g., a 3.55-fold decrease in the TEER value for 0.1% NaTDC). The administration of TDC proliposomes resulted in a 7.1-fold increase in the bioavailability (i.e., 0.49%) of sCT, when administered duodenally to rats. The size of the reconstituted liposomes in water was significantly smaller (e.g., 23.2 nm, number weighted diameter), and the entrapment efficiency (EE) of sCT in the reconstituted liposomes was 2.8-fold larger (54.9%), for TDC proliposomes, compared to proliposomes prepared without NaTDC (sCT proliposomes). CONCLUSION: A 7.1-fold increase in the bioavailability of sCT could be achieved from the TDC proliposomes. In addition to the intrinsic activity of the bile salt to fluidize the membrane, the simultaneous delivery of sCT and NaTDC to the site of absorption in the intestine via proliposomes and the subsequent formation of lipophilic ion-pair complexes between sCT and NaTDC at the site might have been contributing factors in this outstanding absorption enhancement.

Animals↗

PubMed2005

Mechanism of the stationary canalicular excretion of tributylmethyl ammonium in rats with a CCl4-induced acute hepatic injury.

The in vivo canalicular excretion clearance of tributylmethyl ammonium (TBuMA), a P-glycoprotein (P-gp) substrate, was previously reported to be unaffected by the induction of an experimental hepatic injury (EHI) by CCl(4) despite the increased expression of P-gp in the EHI liver. The objective of this study, therefore, was to elucidate the mechanism for the unchanged canalicular excretion clearance of TBuMA in EHI rats. TBuMA uptake was increased in cLPM vesicles from EHI rats compared with that from control rats. The total bile salt concentration in EHI liver was significantly reduced compared with that in a control liver. Because, in our previous studies, the uptake of TBuMA by cLPM vesicles was found to be significantly enhanced in the presence of bile salts, the reduction in bile salt levels in the EHI liver may be related to the unaltered TBuMA clearance. Despite the fact that the uptake of TBuMA by cLPM vesicles was increased by the addition of an EHI liver extract, the extent of the increase was comparatively less compared to the addition of a control liver extract. The in vivo excretion clearance of TBuMA was increased in a taurodeoxycholate dose-dependent manner in EHI rats. These observations suggest, therefore, that despite the induction of P-gp expression by the EHI, the in vivo canalicular excretion clearance of TBuMA remains unaltered as the result of an offset by reduced levels of bile salt(s).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Comparison of pharmacokinetics of loxoprofen and its active metabolites after an intravenous, intramuscular, and oral administration of loxoprofen in rats: evidence for extrahepatic metabolism.

The objective of this study was to characterize the extent of the formation of the active (trans-alcohol form) and inactive (cis-alcohol) metabolites of loxoprofen and to compare the kinetics after its intragastric, intravenous, and intramuscular administrations in rats. After intravenous administration of the drug at doses of 5-20 mg/kg, the clearance and the volume of distribution for loxoprofen, and the ratios of the AUC for the metabolites to the parent drug were not statistically different with the dosage; the formation clearances were 1.08 and 0.87 mL/min/kg for the active and its isomeric metabolite, respectively. After the intragastric, intravenous, or intramuscular administration, AUC for loxoprofen and the metabolites at a dose of 10 mg/kg were not statistically different for the different routes of administration. The formation of the metabolites with the concomitant loss of loxoprofen was found in incubations with liver homogenates and blood but not with a muscle homogenate or plasma, indicating that the conversion of loxoprofen to the metabolites may occur both in the liver and extraheptic tissue(s). Thus, approximately 22% of the loxoprofen may have been converted to the active metabolite in the liver and the extraheptic tissue(s) and the pharmacokinetics of the active metabolite was independent of the route of administration.

Administration, Oral↗

PubMed2005

Dose dependency in the oral bioavailability of an organic cation model, tributylmethyl ammonium (TBuMA), in rats: association with the saturation of efflux by the P-gp system on the apical membrane of the intestinal epithelium.

The oral bioavailability of tributylmethyl ammonium (TBuMA), an organic cation (OC), exhibited a dose-dependency (i.e., 17, 27, and 35% at doses of 0.4, 4, or 12 micromol/kg, respectively) in the rat. Relevant mechanisms were investigated in the present study by estimating the mucosal to serosal (m-s) and serosal to mucosal (s-m) transport of TBuMA across the rat ileum in an Ussing chamber experiment. The m-s permeability rapidly increased with TBuMA concentration in the mucosal side, and then becoming constant at high TBuMA concentrations. Various studies, including temperature- and potential-dependency and inhibition experiments, revealed that carrier-mediated transport mechanisms (most likely OCT1, OCT3, and P-gp) are involved in the s-m transport of TBuMA, and the saturation of the transport at higher concentrations is responsible for the concentration-dependency in the m-s permeability or dose-dependency of the bioavailability of TBuMA. A nonlinear regression of the m-s transport, based on the assumption of a mixed process of linear diffusion and saturable efflux, exhibited a clearance (CLlinear) of 0.343 microL/min/cm2 for the passive diffusion, and an apparent Km of 241 microM for the saturable process. The Km value is consistent with the concentration range in the intestine which is expected to be achieved after the oral dosing of TBuMA at a dose of 0.4 micromol/kg (i.e., 68 approximately 185 microM). Interestingly, the m-s transport of TBuMA was increased by the presence of P-gp substrates or inhibitors in the mucosal side, but not by the mucosal presence of OCT substrates or inhibitors, suggesting that only efflux transport systems on the apical membrane (e.g., P-gp), but not those on the serosal membrane (e.g., OCT1 and OCT3), of the intestinal epithelial cells, are involved in the dose-dependency or concentration dependency. A similar relationship seems likely for drugs that are substrates of efflux transporters on the apical membrane of the intestinal epithelium.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2005

Determination of mequitazine in human plasma by gas-chromatography/mass spectrometry with ion-trap detector and its pharmacokinetics after oral administration to volunteers.

The objective of this study was to develop an assay for mequitazine (MQZ) for the study of the bioavailability of the drug in human subjects. Using one mL of human plasma, the pH of the sample was adjusted and MQZ in the aqueous phase extracted with hexane; the organic layer was then evaporated to dryness, reconstituted and an aliquot introduced to a gas chromatograph/mass spectrometer (GC/MS) system with ion-trap detector. Inter- and intra-day precision of the assay were less than 15.1 and 17.7%, respectively; Inter- and intra-day accuracy were less than 8.91 and 18.6 %, respectively. The limit of quantification for the current assay was set at 1 ng/mL. To determine whether the current assay is applicable in a pharmacokinetic study for MQZ in human, oral formulation containing 10 mg MQZ was administered to healthy male subjects and blood samples collected. The current assay was able to quantify MQZ levels in most of the samples. The maximum concentration (Cmax) was 8.5 ng/mL, which was obtained at 10.1 h, with mean half-life of approximately 45.5 h. Under the current sampling protocol, the ratio of AUCt-->last to AUCt-->infinity was 93.4%, indicating that the blood collection time of 216 h is reasonable for MQZ. Therefore, these observations indicate that an assay for MQZ in human plasma is developed by using GC/MS with ion-trap detector and validated for the study of pharmacokinetics of single oral dose of 10 mg MQZ, and that the current study design for the bioavailability study is adequate for the drug.

Administration, Oral↗

PubMed2005

Effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of organic cations (OCs): selective inhibition of sinusoidal OCs uptake without influencing glucose uptake and canalicular OCs excretion.

The effect of a new hepatoprotective agent, YH-439, on the hepatobiliary transport of a model organic cation (OC), TBuMA (tributylmethylammonium), was investigated. The area under the plasma concentration-time curve (AUC) from time zero to 4 h following iv administration of TBuMA (6.6 micromol/kg) was increased significantly when YH-439 in corn oil (300 mg/kg) was orally administered to rats 24 h prior to the experiment. Nevertheless, the cumulative biliary excretion of TBuMA remained unchanged. As a consequence, the apparent biliary clearance (CLb) of TBuMA was decreased significantly as a result of YH-439 pretreatment, consistent with the fact that the in vivo excretion clearance of TBuMA across the canalicular membrane (CLexc) was not changed by the pretreatment. The in vitro uptake of TBuMA into isolated hepatocytes was decreased by one half by the pretreatment, owing to a decrease in the apparent Vmax and CLlinear, but the Km for the process remained constant. Most interestingly, however, the sinusoidal uptake of glucose, a nutrient, into hepatocytes was not influenced by the pretreatment, suggesting the YH-439 pretreatment specifically impaired the sinusoidal uptake of OCs. Thus, the OC-specific inhibition of hepatic uptake, without influencing the uptake of glucose, a nutrient, appeared to be associated with the hepatoprotective activity of YH-439.

Animals↗

PubMed2005

Transport of anti-allergic drugs across the passage cultured human nasal epithelial cell monolayer.

The purpose of this study was to investigate the nasal absorption characteristics of a series of anti-allergic drugs across the human nasal epithelial cell monolayer, which was passage cultured by the liquid-covered culture (LCC) method on Transwell. Characterization of this cell culture model was achieved by bioelectric measurements and morphological studies. The passages 2--4 of cell monolayers exhibited the TEER value of 1731+/-635 Omega cm(2) after 2 days of seeding and maintained high TEER value for 4--6 days. Morphological study by TEM and SEM showed the existence of the tight junctions, and the cuboidal shaped epithelial cells monolayer. A series of anti-allergic drugs, albuterol hemisulfate, albuterol, fexofenadine HCl, dexamethasone, triamcinolon acetonide, and budesonide were selected as model compounds for transport studies. All the drugs were assayed using reversed-phase HPLC under isocratic conditions. Results indicated that within the logP (apparent 1-octanol/water partition coefficient) range from --1.58 (albuterol) to 3.21 (budesonide), there existed 100-fold difference in the apparent permeability coefficients (P(app)). A log-linear relationship was shown between the drug logP and the P(app) across passaged human nasal epithelial monolayers. The amount of fexofenadine HCl and dexamethasone across passaged human nasal cell monolayers was concentration-dependent in the direction of apical to basolateral. The direction dependent transport studies were investigated among all these drugs and no significant difference in the two directions was observed. In conclusion, this LCC passaged human nasal epithelial culture model may be a useful in vitro model for studying the passive transport processes in nasal drug delivery.

Anti-Allergic Agents↗

PubMed2005

In vitro and in vivo evaluation of a novel nonscrotal matrix-type transdermal delivery system of testosterone.

A matrix-type testosterone (TS) transdermal delivery system for nonscrotal skin was developed with DuroTak 87-2510 as an adhesive polymer. When 3% dodecylamine was used in combination with 10% span 80, the in vitro rat permeation rate increased from 2.29 microg/cm2/hr to 6.51 microg/cm2/ hr as the TS loading dose increased from 2% to 6%. The maximum flux of experimental patch was about 14-fold higher than that of Testoderm. Release kinetics of TS from the patches was proportional to t1/2 following the Higuchi equation, and the release rate of TS increased as TS loading dose increased. Also, a good linear relationship between the skin permeation rate and the release rate was observed, which implies that the release rate is the rate-limiting process of the skin permeation. In vivo study showed that the plasma concentration of TS promptly increased and reached the peak level within 3-6 hours of application of the experimental patch. Area under the curve (AUC0 approximately 48) and Cmax also linearly increased in a dose-dependent manner up to 6% of TS. These results demonstrate the feasibility of developing a nonscrotal matrix-type transdermal delivery system of TS.

Administration, Cutaneous↗

PubMed2005

Limited role of P-glycoprotein in the intestinal absorption of cyclosporin A.

The contribution of P-glycoprotein (P-gp) to the intestinal absorption of cyclosporin A (CsA) was investigated by comparing the in vivo pharmacokinetics of CsA in P-gp knockout mice versus wild-type mice following both oral and intravenous administration and by examining the transport of CsA across Caco-2 cell monolayers. The apparent oral bioavailability of CsA in P-gp knockout mice was 1.55-fold larger than in wild-type mice, leading to an apparent absolute bioavailability of 41.8%. A concentration dependent efflux transport of CsA across Caco-2 cell monolayers was found, which exhibited saturation at a CsA concentration of 1 muM. These results suggest that the involvement of P-gp in the intestinal absorption of CsA is not as profound as was previously thought.

ATP Binding Cassette Transporter, Subfamily B, Mem↗