Biomedical subjects

Kenneth D Chavin

Publications and source records attributed to Kenneth D Chavin.

At least 19 recordsLinked to original sources

PubMed2006

Racial disparities in living kidney donation: is there a lack of willing donors or an excess of medically unsuitable candidates?

BACKGROUND: Live kidney donation is safe for healthy donors and an effective treatment for patients with end-stage renal disease. Many potential donors are referred for live kidney donation, but only a small percentage donate. This study aims to determine reasons for nondonation and establish if racial differences exist. METHODS: A retrospective database and chart review of all patients that were referred for potential live kidney donation from January 1, 2000 to December 31, 2004 was conducted. RESULTS: In all, 30.3% of referred potential live kidney donors were lost to follow-up. Primary reasons for nondonation (n=1,050) included unsuitable donor health (43.1%) and recipient-based causes (41.3%). Immunologic incompatibility accounted for 9.7% of all nondonations. Racial differences indicated more African Americans had incompatible blood types (P=0.01) or ineligible recipients (26.7% vs. 14.4%, P<0.01). More non-African Americans donated (13.2% vs. 4.6%, P<0.01) or were halted because the potential recipient received another organ (living/cadaveric) (20.0% versus 7.9%, P<0.01). Nondonation due to overall donor health (including diabetes and hypertension) did not differ between races, but subanalysis indicated more African American nondonation was due to high body mass index (P=0.01). CONCLUSIONS: Determining the reason behind nondonation is a first step towards understanding low rates of live kidney donation. More African American donor referrals are lost to follow-up while rates of other reasons were similar among races. This may indicate that African Americans are not more frequently medically unsuitable, but that the divergence in rates of live kidney donation is caused by a disparity in willingness to donate among African Americans.

Attitude to Health↗

PubMed2006

Racial differences in coping with the need for kidney transplantation and willingness to ask for live organ donation.

BACKGROUND: Disparities in African-American live donor kidney transplantation continue to grow. How patients cope with the reality of end-stage renal disease and the ensuing need for dialysis or a kidney transplant may directly affect the course of their disease, quality of life, and willingness to ask for live kidney donation. Racial differences in coping may exist and relate to the willingness to ask for live kidney donation. METHODS: The Brief COPE and Living Organ Donor Survey instruments were administered prospectively to potential kidney transplant recipients. The 14 different coping mechanisms were analyzed by race to look for differences. Willingness to ask for live kidney donation was analyzed to look for possible correlations with coping mechanisms and possible predictors analyzed by means of logistic regression. RESULTS: Three hundred thirty-three potential kidney transplant recipients were administered the surveys, with 61% African Americans. Racial differences were seen in the following coping mechanisms: acceptance, humor, religion, denial, and behavioral disengagement. Although racial differences did not exist in overall willingness to ask for donation, positive coping strategies were related to increased willingness to ask for donation. CONCLUSION: African Americans cope with the need for a kidney transplant differently than non-African Americans. Potential African-American kidney recipients are more likely to deny the need for a transplant and are less accepting of their situation. This may affect their perception of the need for transplantation and their persuasiveness in asking for live donations. Transplant programs should ensure that counseling and education programs aim to modify unrealistic expectations and improve recipient coping skills.

Adaptation, Psychological↗

PubMed2006

Healthcare professionals' perceptions of the barriers to living donor kidney transplantation among African Americans.

The number of African Americans participating in living donations continues to remain low. Although researchers have identified multiple barriers to cadaveric donation, relatively little is known about barriers to living kidney donation among this population. We conducted three focus groups of healthcare professionals from a transplant center in South Carolina to determine their perceptions of barriers to living kidney donation among African Americans. An African-American and a Caucasian member of the project team facilitated the groups. Sessions were taped, transcribed and analyzed for key themes. Eighteen transplant professionals participated in the three focus groups, including physicians, transplant coordinators, pharmacists and a data coordinator. Analysis of the transcripts revealed the following perceived barriers to living kidney donation among African Americans: 1) pre-existing medical conditions, 2) financial concerns, 3) reluctance to ask family members and/or friends, 4) distrust of the medical community, 5) fear of surgery, and 6) lack of awareness about living donor kidney transplantation. In addition to previously described barriers to cadaveric donation, this study identified barriers unique to living donation, such as pre-existing medical conditions, financial concerns, reluctance to ask a living donor and fear of surgery.

Black or African American↗

PubMed2006

Obesity alters rat abdominal flap survival.

Obesity presents a risk factor for flap-related complications in autologous tissue breast reconstruction. In this study, an animal model was developed to examine this phenomenon. Abdominal flaps based on a superficial inferior epigastric pedicle were elevated in an experimental group of obese Zucker (fa/fa) rats (n = 8; mean weight, 413 g) and in their lean littermates (n = 9; mean weight, 276 g). Flap tissue was harvested from a subset of both groups for baseline characterization, including histology, and assays for ATP and oxidative phosphorylation uncoupler, UCP-2. Flaps were then evaluated for survival by planimetry at 4 and 7 days postprocedure. Flap survival 7 days postoperatively was reduced in obese (42.0% +/- 8.6%) versus lean (70.3% +/- 6.7%) rats (P < 0.05). At baseline, flap tissue of obese animals had decreased ATP content relative to lean counterparts (0.12 +/- 0.12 nM/microg vs 0.36 +/- 0.23 nM/microg protein, P < 0.05), whereas UCP2 mRNA was higher in obese flap tissue versus lean. Reduced viability of obese flaps may be attributable to decreased baseline energy stores due to oxidative phosphorylation uncoupling by UCP-2. This study is the first to introduce a promising animal model for examining the effect of obesity on increased flap-related complications in breast reconstruction using autologous tissue.

Abdomen↗

PubMed2005

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes?

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Biopsy↗

PubMed2005

Growth differentiation factor-15: induction in liver injury through p53 and tumor necrosis factor-independent mechanisms.

Expression of macrophage inhibitory cytokine-1 (MIC-1), a divergent transforming growth factor-beta family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15), is induced in hepatocytes by surgical and chemical injury and heat shock. Here, we demonstrate that the regulation of GDF-15/MIC-1 expression may be evolutionarily conserved because MIC-1 was induced in diseased human livers. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although tumor necrosis factor (TNF) induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtypes. Furthermore, although the stress sensor p53 is known to induce GDF-15/MIC-1 expression, injury-elicited Gdf15 expression was unchanged in p53 null mice. Our results demonstrate that GDF-15 induction is an immediate early response to liver injury that can occur through TNF and p53 independent pathways.

Animals↗

PubMed2005

Short-term administration of (-)-epigallocatechin gallate reduces hepatic steatosis and protects against warm hepatic ischemia/reperfusion injury in steatotic mice.

Hepatic steatosis increases the extent of cellular injury incurred during ischemia/reperfusion (I/R) injury. (-)-Epigallocatechin gallate (EGCG), the major flavonoid component of green tea (camellia sinensis) is a potent antioxidant that inhibits fatty acid synthase (FAS) in vitro. We investigated the effects of EGCG on hepatic steatosis and markers of cellular damage at baseline and after I/R injury in ob/ob mice. Animals were pretreated with 85 mg/kg EGCG via intraperitoneal (ip) injection for 2 days or oral consumption in the drinking water for 5 days before 15 minutes of warm ischemia and 24 hours of reperfusion. After EGCG administration, total baseline hepatic fat content decreased from baseline. Palmitic acid and linoleic acid levels also were reduced substantially in all ECGC-treated animals before I/R. Alanine aminotransferase (ALT) levels decreased in all EGCG-treated animals compared with control animals after I/R. Histologic analysis demonstrated an average decrease of 65% necrosis after EGCG administration. EGCG administration also increased resting hepatic energy stores as determined by an increase in cellular adenosine triphosphate (ATP) with a concomitant decrease in uncoupling protein 2 (UCP2) before I/R. Finally, there was an increased level of glutathione (GSH) in the EGCG-treated mice compared with the vehicle-treated mice both at baseline and after I/R. In conclusion, taken together, this study demonstrates that treatment with ECGC by either oral or ip administration, significantly protects the liver after I/R, possibly by reducing hepatic fat content, increasing hepatic energy status, and functioning as an antioxidant.

Animals↗

PubMed2005

Effects of St John's wort (Hypericum perforatum L.) extract on plasma androgen concentrations in healthy men and women: a pilot study.

St John's wort extract (SJW; Hypericum perforatum L.) is taken extensively as a putative herbal antidepressant. It has been shown to induce the activity of cytochrome P-450 3A4 (CYP3A4) and to increase the clearance of numerous drugs and steroids such as cortisol and ethinyl estradiol. This study was conducted to determine if SJW exposure also alters the concentrations of circulating androgenic steroid hormones. The study was conducted using healthy volunteers (6M, 6F) studied before and after a 14-day treatment period with a SJW preparation previously demonstrated to induce the activity of CYP3A4. Plasma concentrations of testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG) and the combined concentrations of androsterone sulfate (AoS) and epiandrosterone sulfate (epiAoS) were measured by immunoassay methods. The results of analysis demonstrated that SJW did not significantly alter the majority of the androgens studied (p > 0.05) although the combined concentrations of the 5alpha-reduced steroids, AoS and epiAoS, significantly declined following treatment in all subjects (p = 0.02), and in males (p = 0.04). Furthermore, the testosterone to DHT ratio was increased in both men and women. Although the latter increase did not reach statistical significance, it is also consistent with the possible inhibition of 5alpha-reductase by SJW. It is concluded that despite significant induction of CYP3A4, short term administration of SJW does not significantly alter the concentrations of most circulating androgens in men and women but may produce a dimunition in some of the circulating 5alpha-reduced androgens.

Adult↗

PubMed2005

Oral administration of a decaffeinated green tea (Camellia sinensis) extract did not alter urinary 8-epi-prostaglandin F(2 alpha), a biomarker for in-vivo lipid peroxidation.

Oxidative stress is involved in the pathogenesis of numerous chronic human diseases. The objective of this study was to determine whether administration of a decaffeinated green tea extract providing 844 mg flavonoids daily reduced the urinary excretion of 8-epi-prostaglandin F(2 alpha) (8-epi-PGF(2 alpha)), a product of lipid peroxidation in cellular membranes and of low-density lipoprotein (LDL). Nine healthy male and female subjects were studied at baseline and after 14 days of green tea supplementation. Analysis of urinary 8-epi-PGF(2 alpha) was performed using immunoaffinity extraction-gas chromatography-negative ion chemical ionization-mass spectrometry (GC-NICI-MS). Urinary 8-epi-PGF(2 alpha) concentrations were 0.286+/-0.120 nmol (mmol creatinine)(-1) at baseline and 0.244+/-0.177 nmol mmol(-1) creatinine after green tea supplementation. There were no significant differences in the excretion of urinary 8-epi-PGF(2 alpha) after treatment with green tea. We conclude that 14 days of green tea supplementation did not significantly alter in-vivo lipid peroxidation.

Administration, Oral↗

PubMed2005

Effect of Ginkgo biloba extract on plasma steroid concentrations in healthy volunteers: a pilot study.

STUDY OBJECTIVE: To determine if a standardized ginkgo supplement significantly alters concentrations of circulating androgenic steroids in humans. DESIGN: Open-label, fixed-treatment order, crossover study. SETTING: University general clinical research center. SUBJECTS: Eleven healthy volunteers (six men, five women). INTERVENTION: Volunteers received ginkgo biloba 240 mg/day for 14 days. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cortisol, 11-deoxycortisol, 17alpha-hydroxyprogesterone, testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, androstenedione, and free testosterone, as well as free androgen index and combined concentrations of androsterone sulfate and epiandrosterone sulfate, were analyzed in all subjects before and after their 14-day course of ginkgo biloba. Ginkgo biloba did not significantly alter endogenous steroid levels compared with baseline values (p < 0.05). CONCLUSION: A 14-day oral administration of a widely used, standardized ginkgo extract at a generally advocated dosage of 240 mg/day did not significantly alter concentrations of major circulating steroids in men and women.

Adult↗

PubMed2004

Localization of ABCG5 and ABCG8 proteins in human liver, gall bladder and intestine.

BACKGROUND: The molecular mechanisms that regulate the entry of dietary sterols into the body and their removal via hepatobiliary secretion are now beginning to be defined. These processes are specifically disrupted in the rare autosomal recessive disease, Sitosterolemia (MIM 210250). Mutations in either, but not both, of two genes ABCG5 or ABCG8, comprising the STSL locus, are now known to cause this disease and their protein products are proposed to function as heterodimers. Under normal circumstances cholesterol, but not non-cholesterol sterols, is preferentially absorbed from the diet. Additionally, any small amounts of non-cholesterol sterols that are absorbed are rapidly taken up by the liver and preferentially excreted into bile. Based upon the defects in sitosterolemia, ABCG5 and ABCG8 serve specifically to exclude non-cholesterol sterol entry at the intestinal level and are involved in sterol excretion at the hepatobiliary level. METHODS: Here we report the biochemical and immuno-localization of ABCG5 and ABCG8 in human liver, gallbladder and intestine using cell fractionation and immunohistochemical analyses. RESULTS: We raised peptide antibodies against ABCG5 and ABCG8 proteins. Using human liver samples, cell fractionation studies showed both proteins are found in membrane fractions, but they did not co-localize with caveolin-rafts, ER, Golgi or mitochondrial markers. Although their distribution in the sub-fractions was similar, they were not completely contiguous. Immunohistochemical analyses showed that while both proteins were readily detectable in the liver, ABCG5 was found predominately lining canalicular membranes, whereas ABCG8 was found in association with bile duct epithelia. At the cellular level, ABCG5 appeared to be apically expressed, whereas ABCG8 had a more diffuse expression pattern. Both ABCG5 and ABCG8 appeared to localize apically as shown by co-localization with MRP2. The distribution patterns of ABCG5 and ABCG8 in the gallbladder were very similar to each other. In the small intestine both ABCG5 and ABCG8 appear to line the brush border. However, at the level of the enterocyte, the cellular distribution patterns of ABCG5 and ABCG8 differed, such that ABCG5 was more diffuse, but ABCG8 was principally apical. Using standard deglycosylation methods, ABCG5 and ABCG8 do not appear to be glycosylated, suggesting a difference between human and mouse proteins. CONCLUSION: We report the distribution patterns of ABCG5 and ABCG8 in human tissues. Cell fractionation studies showed that both proteins co-fractionated in general, but could also be found independent of each other. As predicted, they are expressed apically in both intestine and liver, although their intracellular expression patterns are not completely congruent. These studies support the concept of heterodimerization of ABCG5 and ABCG8, but also support the notion that these proteins may have an independent function.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2004

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation.

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.

Child↗

PubMed2004

Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers.

Valerian (Valeriana officinalis) is a popular dietary supplement. The objective of this study was to assess the influence of a valerian extract on the activity of the drug-metabolizing enzymes cytochrome P450 2D6 (CYP2D6) and 3A4. Probe drugs dextromethorphan (30 mg; CYP2D6 activity) and alprazolam (2 mg; CYP3A4 activity) were administered orally to healthy volunteers (n = 12) at baseline and again after exposure to two 500-mg valerian tablets (1000 mg) nightly for 14 days. The valerian supplement contained a total valerenic acid content of 5.51 mg/tablet. Dextromethorphan to dextorphan metabolic ratios (DMRs) and alprazolam pharmacokinetics were determined at baseline and after valerian treatment. The DMR was 0.214 +/- 0.025 at baseline and 0.254 +/- 0.026 after valerian supplementation (p > 0.05). For alprazolam, the maximum concentration in plasma was significantly increased after treatment with valerian (25 +/- 7 ng/ml versus 31 +/- 8 ng/ml; p < 0.05). There were no significant differences in other pharmacokinetic parameters at baseline and after valerian exposure (all p values > or = 0.05; time to reach maximum concentration in plasma, 3.0 +/- 3.2 versus 3.1 +/- 2.1 h; area under the plasma concentration versus time curve, 471 +/- 183 versus 539 +/- 240 hx ng x ml(-1); half-life of elimination, 13.5 +/- 4.3 versus 12.2 +/- 5.6 h). Our results indicate that although a modest increase was observed in the alprazolam Cmax, typical doses of valerian are unlikely to produce clinically significant effects on the disposition of medications dependent on the CYP2D6 or CYP3A4 pathways of metabolism.

Adult↗

PubMed2004

Steatotic liver transplantation in the mouse: a model of primary nonfunction.

BACKGROUND: The number of potential donor organs deemed suboptimal for transplantation because of hepatic steatosis is rising as the obesity rate increases. However, no mouse transplant model has been described within the framework of hepatic steatosis. We describe the development of and our initial experience with a steatotic mouse orthotopic liver transplant model using the ob/ob mouse. This model is technically achievable and functionally mimics primary nonfunction. MATERIALS AND METHODS: Adapting techniques of a nonarterialized murine transplant model, C57BL6 ob/ob mice aged 5-7 weeks (26-35 g) and lean controls served as liver donors and recipients. Orthotopic liver transplantation (OLT) was performed using a two-cuff technique at the infrahepatic cava and portal vein. The suprahepatic cava was anastomosed end to end, and the bile duct was stented. The hepatic artery was not reconstructed. RESULTS: Lean-to-lean OLT was performed with 70% (n = 10) long-term survival. ob/ob-to-age-matched lean recipients had 0% (n = 10) survival because of size discrepancy. ob/ob livers were transplanted to size-matched lean recipients (>3 months old) with short-term survival of 30% (n = 10). These mice survived the operation, awakened, but expired within 24 h. Serum transaminases revealed a significantly higher injury profile in the recipients of the steatotic livers, and histology showed massive centrilobular coagulative necrosis with hemorrhage, the overall picture being that of primary nonfunction. CONCLUSIONS: This novel use of the ob/ob mouse for OLT provides us with a model for steatotic transplantation with primary nonfunction as the end point and may help to better understand the response of the steatotic liver to the insult of transplantation.

Animals↗

PubMed2004

Development of an unbiased method for the estimation of liver steatosis.

BACKGROUND: Steatosis significantly contributes to an organ's transplantability. Livers with >30% fat content have a 25% chance of developing primary non-function (PNF). The current practice of evaluating a hematoxylin and eosin (H&E) stained donor biopsy by visual interpretation is subjective. We hypothesized that H&E staining of frozen sections fails to accurately estimate the degree of steatosis present within a given liver biopsy. To address this problem of evaluating steatosis in prospective donor organs, we developed a fast, user friendly computer methodology to objectively assess fat content based on the differential quantification of color pixels in Oil Red O (ORO) stained liver biopsies. METHODS: The accuracy of human visual estimation of fat content by H&E and ORO stains was compared with computer-based measurements of the same slides from 25 frozen sections of donor biopsies. RESULTS: Samples with a fat content >20% showed marked variation between human interpretation and computer analysis. There was also a significant difference in the human interpretation of fat based on the method of staining. This difference ranged from 3 to 37% with H&E. DISCUSSION: Use of ORO resulted in a more consistent estimation of liver steatosis compared with H&E, but human interpretations failed to correlate with computer measurements. Such differences in fat content estimations might result in the rejection of a potentially transplantable organ or the acceptance of a marginal one. Ideally, our protocol can rapidly be applied to clinical practice for accurate and consistent measurement of fat in liver sections for the ultimate purpose of increasing the number of successful transplantable organs.

Algorithms↗

PubMed2004

Fatty acid synthase blockade protects steatotic livers from warm ischemia reperfusion injury and transplantation.

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARalpha, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.

Adenosine Triphosphate↗

PubMed2004

Anti-endotoxin monoclonal antibodies are protective against hepatic ischemia/reperfusion injury in steatotic mice.

Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti-LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta-hepatis occlusion and varying lengths of reperfusion with or without pre-treatment with an anti-LPS mAb. There was 14-31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75-83% of ob/ob mice pre-treated with an anti-LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti-LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti-LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.

Animals↗

PubMed2004

Green tea (Camellia sinensis) extract does not alter cytochrome p450 3A4 or 2D6 activity in healthy volunteers.

Green tea extract is a widely used dietary supplement. The objective of this study was to assess the influence of a decaffeinated green tea (DGT; Camellia sinensis) extract on the activity of the drug-metabolizing enzymes cytochrome P-450 2D6 and 3A4. Probe drugs dextromethorphan (30 mg, CYP2D6 activity) and alprazolam (ALPZ; 2 mg, CYP3A4 activity) were administered orally to healthy volunteers (n = 11) at baseline, and again after treatment with four DGT capsules/day for 14 days. Each DGT capsule contained 211 +/- 25 mg of green tea catechins and <1 mg of caffeine. Dextromethorphan metabolic ratios (DMRs) and alprazolam pharmacokinetics were determined at baseline and after DGT treatment. There were no significant differences in ALPZ pharmacokinetics at baseline and after DGT treatment (all P values >/= 0.05; maximum concentration in plasma, 33 +/- 8 versus 34 +/- 13 ng/ml; time to reach maximum concentration in plasma, 1.4 +/- 1.2 versus 1.4 +/- 1.2 h; area under the plasma concentration versus time curve, 480 +/- 119 versus 510 +/- 107 h. ng. ml(-1); half-life of elimination, 12.3 +/- 1.7 versus 13.1 +/- 3.4 h). The DMR was 0.053 +/- 0.045 at baseline and 0.041 +/- 0.032 after DGT supplementation (P > 0.05). The plasma concentration of the green tea flavonoid, (-)-epigallocatechin gallate, reached 1.3 +/- 1.8 microM 2 h after DGT treatment. Our results indicate that DGT is unlikely to alter the disposition of medications primarily dependent on the CYP2D6 or CYP3A4 pathways of metabolism.

Administration, Oral↗