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Eduardo Bruera - One of the best experts on this subject based on the ideXlab platform.

  • switching from methadone to a different opioid what is the equianalgesic Dose Ratio
    Journal of Palliative Medicine, 2008
    Co-Authors: Paul Walker, Guddi Kaur, Karen Zhang, Jeanine Hanohano, Mark F Munsell, Shana L Palla, Eduardo Bruera
    Abstract:

    Abstract Introduction: Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. However, in the management of cancer pain with strong opioids, rotation to a different opioid (opioid rotation) may be required because of side effects or poor pain control. Rotation from methadone to another opioid has received limited study and therefore may be difficult because of the absence of a uniformly accepted Dose conversion Ratio. Methods: Retrospectively reviewed consecutive medical records of patients undergoing an opioid rotation from methadone to an alternative opioid were evaluated. For inclusion, patients were required to have received methadone for at least 3 days and have reached stable Dose of the alternative opioid(s) during the 7 days following. Stable Dose was defined as a 30% or less change in opioid Dose from one day to the next. Results: Records of 39 patients met inclusion criteria. Excluded from analysis were 5 patients who were restarted on methadone within 7 days, 2 w...

  • switching from methadone to a different opioid what is the equianalgesic Dose Ratio
    Journal of Clinical Oncology, 2006
    Co-Authors: Paul Walker, Guddi Kaur, Karen Zhang, H Jeanine, Eardie Curry, Shana L Palla, Eduardo Bruera, M Mansell
    Abstract:

    8617 Background: Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. However, the rotation from ME to another opioid may be difficult because of the absence of a ...

  • Dose Ratio between morphine and methadone in patients with cancer pain a retrospective study
    Cancer, 1998
    Co-Authors: Peadar G. Lawlor, John Hanson, Kenneth Turner, Eduardo Bruera
    Abstract:

    BACKGROUND Current equianalgesic reference tables, based largely on single Dose studies, give Dose Ratios of 1:1 to 4:1 for oral morphine to oral methadone, which possibly are inaccurate in patients with cancer pain who are exposed to multiple Doses of these opioids. The purpose of this study was to determine the equianalgesic Dose Ratio between morphine and methadone in patients with cancer pain and to establish whether the Dose Ratio changes as a function of previous opioid Dose. METHODS A retrospective analysis of consecutive rotations involving morphine and methadone using standard selection criteria identified a total of 20 evaluable rotations (14 from morphine to methadone and 6 from methadone to morphine). Opioid Doses and pain intensity levels pre- and postrotation were analyzed. RESULTS Median Dose Ratios (lower-upper quartiles) for morphine to methadone and methadone to morphine rotations were 11.36 (range, 5.98-16.27) and 8.25 (range, 4.37-11.3), respectively (P = 0.23). Combining all 20 rotations, a unified median Dose Ratio of 11.2 (range, 5.06-13.24) was calculated. There was no significant difference in pain intensity levels pre- and postrotation as recorded on a visual analogue scale. Univariate correlational analysis of Dose Ratio and the level of daily morphine Dose prior to rotation revealed a Spearman correlation coefficient of 0.86 (P = 0.0001). In patients receiving >1165 mg per day prior to methadone rotation, a median Dose Ratio of 16.84 (range, 12.25-87.95) was observed, which was approximately 3 times higher compared with a median Dose Ratio of 5.42 (range, 2.95-9.09) (P = 0.007) for the 50% of patients receiving lower morphine Doses. CONCLUSIONS The results highlight the general underestimation of methadone potency and the consequent risk of potential life-threatening toxicity. The strongly positive correlation between Dose Ratio and previous morphine Dose suggests the need for a highly individualized and cautious approach when rotating from morphine to methadone in patients with cancer pain. Cancer 1998;82:1167-73. © 1998 American Cancer Society.

  • Dose Ratio between morphine and methadone in patients with cancer pain a retrospective study
    Cancer, 1998
    Co-Authors: Peadar G. Lawlor, John Hanson, Kenneth Turner, Eduardo Bruera
    Abstract:

    BACKGROUND Current equianalgesic reference tables, based largely on single Dose studies, give Dose Ratios of 1:1 to 4:1 for oral morphine to oral methadone, which possibly are inaccurate in patients with cancer pain who are exposed to multiple Doses of these opioids. The purpose of this study was to determine the equianalgesic Dose Ratio between morphine and methadone in patients with cancer pain and to establish whether the Dose Ratio changes as a function of previous opioid Dose. METHODS A retrospective analysis of consecutive rotations involving morphine and methadone using standard selection criteria identified a total of 20 evaluable rotations (14 from morphine to methadone and 6 from methadone to morphine). Opioid Doses and pain intensity levels pre- and postrotation were analyzed. RESULTS Median Dose Ratios (lower-upper quartiles) for morphine to methadone and methadone to morphine rotations were 11.36 (range, 5.98-16.27) and 8.25 (range, 4.37-11.3), respectively (P = 0.23). Combining all 20 rotations, a unified median Dose Ratio of 11.2 (range, 5.06-13.24) was calculated. There was no significant difference in pain intensity levels pre- and postrotation as recorded on a visual analogue scale. Univariate correlational analysis of Dose Ratio and the level of daily morphine Dose prior to rotation revealed a Spearman correlation coefficient of 0.86 (P = 0.0001). In patients receiving >1165 mg per day prior to methadone rotation, a median Dose Ratio of 16.84 (range, 12.25-87.95) was observed, which was approximately 3 times higher compared with a median Dose Ratio of 5.42 (range, 2.95-9.09) (P = 0.007) for the 50% of patients receiving lower morphine Doses. CONCLUSIONS The results highlight the general underestimation of methadone potency and the consequent risk of potential life-threatening toxicity. The strongly positive correlation between Dose Ratio and previous morphine Dose suggests the need for a highly individualized and cautious approach when rotating from morphine to methadone in patients with cancer pain. Cancer 1998;82:1167-73. © 1998 American Cancer Society.

  • equianalgesic Dose Ratio between methadone and other opioid agonists in cancer pain comparison of two clinical experiences
    Annals of Oncology, 1998
    Co-Authors: Carla Ripamonti, L Groff, F De Conno, John Hanson, Jose Pereira, Martin Belzile, Eduardo Bruera
    Abstract:

    Summary Background Oral methadone is considered to be a valid opioid analgesic alternative to morphine and hydromorphone in treating cancer pain. However, the use of methadone could be complicated by the limited knowledge of the equianalgesic Dose/Ratio with the other analgesic opioids when switching in tolerant patients. Patients and methods In two Palliative Care Units, data collected regarding 88 advanced cancer patients with pain switched from different opioids to oral methadone were reviewed and compared with the aim of determining the equianalgesic Dose Ratio in relation to the Dose of opioid previously administered. Results The results of this retrospective study suggest that: (1) methadone is much more potent than previously described in literature, (2) the Dose Ratio between hydromorphone and methadone is higher than as suggested by equianalgesic tables, and (3) the Ratio correlates with total opioid Dose administered before switching. Conclusions The fact that methadone Ratio is different according to the opioid Dose used previously should be taken into careful consideRation by the clinician in order to avoid severe toxicity or death during switchover. Prospective studies should be carried out in order to better define our findings.

Eric Thervet - One of the best experts on this subject based on the ideXlab platform.

  • impact of cytochrome p450 3a5 genetic polymorphism on tacrolimus Doses and concentRation to Dose Ratio in renal transplant recipients
    Transplantation, 2003
    Co-Authors: Eric Thervet, Dany Anglicheau, Barry P King, Mariehelene Schlageter, Bruno Cassinat, Philippe Beaune, Christophe Legendre, Ann K Daly
    Abstract:

    Background Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. Methods CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus Dose and concentRation-to-Dose Ratio. Results The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean Doses required to obtain the targeted concentRation-to-Dose Ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. Conclusions Determination of CYP3A5 genotype is predictive of the Dose of tacrolimus in renal transplant recipients and may help to determine the initial daily Dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

  • association of the multidrug resistance 1 gene single nucleotide polymorphisms with the tacrolimus Dose requirements in renal transplant recipients
    Journal of The American Society of Nephrology, 2003
    Co-Authors: Dany Anglicheau, Mariehelene Schlageter, Bruno Cassinat, Philippe Beaune, Christophe Legendre, Celine Verstuyft, Pierre Laurentpuig, Laurent Becquemont, Eric Thervet
    Abstract:

    ABSTRACT. The immunosuppressive drug tacrolimus, whose pharmacokinetic characteristics display large interindividual variations, is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 ( MDR1 ) gene. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. Because P-gp is known to control tacrolimus intestinal absorption, it was postulated that these polymorphisms are associated with tacrolimus pharmacokinetic variations in renal transplant recipients. The objective of this study was to evaluate in a retrospective study of 81 renal transplant recipients the effect on tacrolimus dosages and concentRation/Dose Ratio of four frequent MDR1 SNP possibly associated with P-gp function (T-129C in exon 1b, 1236C>T in exon 12, 2677G>T,A in exon 21, and 3435C>T in exon 26). As in the general population, the SNP in exons 12, 21, and 26 were frequent (16, 17.3, and 22.2% for the variant homozygous genotype, respectively) and exhibited incomplete linkage disequilibrium. One month after tacrolimus introduction, exon 21 SNP correlated significantly with the daily tacrolimus Dose ( P ≤ 0.05) and the concentRation/Dose Ratio ( P ≤ 0.02). Tacrolimus Dose requirements were 40% higher in homozygous than wild-type patients for this SNP. The concentRation/Dose Ratio was 36% lower in the wild-type patients, suggesting that, for a given Dose, their tacrolimus blood concentRation is lower. Haplotype analysis substantiated these results and suggested that exons 26 and 21 SNP may be associated with tacrolimus Dose requirements. Genotype monitoring of the MDR1 gene reliably predicts the optimal Dose of tacrolimus in renal transplant recipients and may predict the initial daily Dose needed by individual patients to obtain adequate immunosuppression. E-mail: Dany.Anglicheau@biomedicale. univ-paris5.fr

Satohiro Masuda - One of the best experts on this subject based on the ideXlab platform.

  • impact of cyp3a5 por and cyp2c19 polymorphisms on trough concentRation to Dose Ratio of tacrolimus in allogeneic hematopoietic stem cell transplantation
    International Journal of Molecular Sciences, 2019
    Co-Authors: Kimitaka Suetsugu, Yasuo Mori, Nanae Yamamoto, Tomohiro Shigematsu, Toshihiro Miyamoto, Nobuaki Egashira, Koichi Akashi, Satohiro Masuda
    Abstract:

    Single nucleotide polymorphisms in drug-metabolizing genes may affect tacrolimus pharmacokinetics. Here, we investigated the influence of genotypes of CYP3A5, CYP2C19, and POR on the concentRation/Dose (C/D) Ratio of tacrolimus and episodes of acute graft-versus-host disease (GVHD) in Japanese recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty-six patients receiving the first HSCT using tacrolimus-based GVHD prophylaxis were enrolled with written informed consent. During continuous intravenous infusion, HSCT recipients carrying the CYP3A5*1 allele, particularly those with at least one POR*28 allele, had a significantly lower tacrolimus C/D Ratio throughout all three post-HSCT weeks compared to that in recipients with POR*1/*1 (p < 0.05). The CYP3A5*3/*3 genotype and the concomitant use of voriconazole were independent predictors of an increased tacrolimus C/D Ratio during the switch from continuous intravenous infusion to oral administRation (p < 0.05). In recipients receiving concomitant administRation of voriconazole, our results suggest an impact of not only CYP3A5 and CYP2C19 genotypes, but also plasma voriconazole concentRation. Although switching from intravenous to oral administRation at a Ratio of 1:5 was seemingly appropriate in recipients with CYP3A5*1, a lower conversion Ratio (1:2–3) was appropriate in recipients with CYP3A5*3/*3. Our results suggest that CYP3A5, POR, and CYP2C19 polymorphisms are useful biomarkers for individualized dosage adjustment of tacrolimus in HSCT recipients.

  • interaction between tacrolimus and lansoprazole but not rabeprazole in living donor liver transplant patients with defects of cyp2c19 and cyp3a5
    Drug Metabolism and Pharmacokinetics, 2008
    Co-Authors: Keiko Hosohata, Satohiro Masuda, Shinji Uemoto, Yasuhiro Ogura, Fumitaka Oike, Yasutsugu Takada, Toshiya Katsura, Kenichi Inui
    Abstract:

    We report different effects of administRation of proton pump inhibitors on tacrolimus blood concentRation in two living-donor liver transplant patients. In case 1, a 51-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation, and tacrolimus was orally administered. Omeprazole (40 mg/day) was introduced intravenously between postoperative days 5 and 6, and oral lansoprazole (30 mg/day) was introduced from day 6, leading to an increase in the concentRation/Dose Ratio of tacrolimus from day 10. In case 2, a 41-year-old living-donor liver transplant woman received tacrolimus, and co-administered with omeprazole (40 mg/day) intravenously during 7 days immediately after surgery. During this period, trough concentRation of tacrolimus was high, but the concentRation/Dose Ratio of tacrolimus was gradually decreasing with time. Switched to rabeprazole (10 mg/day) orally on the postoperative 8th day, the concentRation/Dose Ratio of tacrolimus remained low, indicating little drug-drug interaction between tacrolimus and rabeprazole. In both cases, the genotypes of CYP2C19 and CYP3A5 were defective both in the graft liver and in the native intestine. A drug-drug interaction between rabeprazole and tacrolimus was not observed in this case study presented, suggesting that this combination could be safely used in tacrolimus therapy after liver transplantation.

  • cyp3a5 1 carrying graft liver reduces the concentRation oral Dose Ratio of tacrolimus in recipients of living donor liver transplantation
    Pharmacogenetics, 2004
    Co-Authors: Maki Goto, Satohiro Masuda, Tetsuya Kiuchi, Koichi Tanaka, Yasuhiro Ogura, Fumitaka Oike, Masahiro Okuda, Kenichi Inui
    Abstract:

    ObjectivesTacrolimus is widely used for immunosuppressive therapy after organ transplantation, but its pharmacokinetics shows such great interindividual variation that control of its blood concentRation is difficult. We have previously reported that an intestinal P-glycoprotein (MDR1) contributes to

  • c3435t polymorphism in the mdr1 gene affects the enterocyte expression level of cyp3a4 rather than pgp in recipients of living donor liver transplantation
    Pharmacogenetics, 2002
    Co-Authors: Maki Goto, Satohiro Masuda, Hideyuki Saito, Shinji Uemoto, Tetsuya Kiuchi, Koichi Tanaka, Kenichi Inui
    Abstract:

    The bioavailability of structurally unrelated drugs is limited by active secretion via the multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) from enterocyte into lumen as well as intestinal metabolism by cytochrome P450 IIIA4 (CYP3A4). In the present study, we analyzed whether genetic polymorphism of the MDR1 had some influence on the intestinal expression levels of Pgp and CYP3A4 and the tacrolimus concentRation/Dose Ratio over the first postoperative days in recipients of living-donor liver transplantation (LDLT). Genotyping assays were performed for the major 10 polymorphisms in the MDR1 gene by the polymerase chain reaction-restriction enzyme length polymorphism method. The allele frequencies of variations at five positions were almost comparable with those in the former studies in Caucasians and Japanese, but there was no variation at the other five positions. Although no polymorphism correlated with the intestinal expression of MDR1 mRNA or the tacrolimus concentRation/Dose Ratio in the LDLT recipients, the C3435T polymorphism significantly affected the intestinal expression level of CYP3A4 mRNA as follows; 3435C/C>3435C/T (P 3435T/T (P < 0.01 vs. 3435C/C). Therefore, the identified polymorphisms including C3435T in the MDR1 gene were indicated to have no influence on the intestinal expression level of Pgp or the tacrolimus concentRation/Dose Ratio in the recipients of LDLT. On the other hand, the C3435T polymorphism of MDR1 was suggested to correlate with the enterocyte expression of CYP3A4 rather than Pgp linking unknown genetic variation in CYP3A4 gene.

Kenichi Inui - One of the best experts on this subject based on the ideXlab platform.

  • interaction between tacrolimus and lansoprazole but not rabeprazole in living donor liver transplant patients with defects of cyp2c19 and cyp3a5
    Drug Metabolism and Pharmacokinetics, 2008
    Co-Authors: Keiko Hosohata, Satohiro Masuda, Shinji Uemoto, Yasuhiro Ogura, Fumitaka Oike, Yasutsugu Takada, Toshiya Katsura, Kenichi Inui
    Abstract:

    We report different effects of administRation of proton pump inhibitors on tacrolimus blood concentRation in two living-donor liver transplant patients. In case 1, a 51-year-old man with liver cirrhosis due to hepatitis C virus underwent living-donor liver transplantation, and tacrolimus was orally administered. Omeprazole (40 mg/day) was introduced intravenously between postoperative days 5 and 6, and oral lansoprazole (30 mg/day) was introduced from day 6, leading to an increase in the concentRation/Dose Ratio of tacrolimus from day 10. In case 2, a 41-year-old living-donor liver transplant woman received tacrolimus, and co-administered with omeprazole (40 mg/day) intravenously during 7 days immediately after surgery. During this period, trough concentRation of tacrolimus was high, but the concentRation/Dose Ratio of tacrolimus was gradually decreasing with time. Switched to rabeprazole (10 mg/day) orally on the postoperative 8th day, the concentRation/Dose Ratio of tacrolimus remained low, indicating little drug-drug interaction between tacrolimus and rabeprazole. In both cases, the genotypes of CYP2C19 and CYP3A5 were defective both in the graft liver and in the native intestine. A drug-drug interaction between rabeprazole and tacrolimus was not observed in this case study presented, suggesting that this combination could be safely used in tacrolimus therapy after liver transplantation.

  • cyp3a5 1 carrying graft liver reduces the concentRation oral Dose Ratio of tacrolimus in recipients of living donor liver transplantation
    Pharmacogenetics, 2004
    Co-Authors: Maki Goto, Satohiro Masuda, Tetsuya Kiuchi, Koichi Tanaka, Yasuhiro Ogura, Fumitaka Oike, Masahiro Okuda, Kenichi Inui
    Abstract:

    ObjectivesTacrolimus is widely used for immunosuppressive therapy after organ transplantation, but its pharmacokinetics shows such great interindividual variation that control of its blood concentRation is difficult. We have previously reported that an intestinal P-glycoprotein (MDR1) contributes to

  • c3435t polymorphism in the mdr1 gene affects the enterocyte expression level of cyp3a4 rather than pgp in recipients of living donor liver transplantation
    Pharmacogenetics, 2002
    Co-Authors: Maki Goto, Satohiro Masuda, Hideyuki Saito, Shinji Uemoto, Tetsuya Kiuchi, Koichi Tanaka, Kenichi Inui
    Abstract:

    The bioavailability of structurally unrelated drugs is limited by active secretion via the multidrug resistance gene (MDR1) product P-glycoprotein (Pgp) from enterocyte into lumen as well as intestinal metabolism by cytochrome P450 IIIA4 (CYP3A4). In the present study, we analyzed whether genetic polymorphism of the MDR1 had some influence on the intestinal expression levels of Pgp and CYP3A4 and the tacrolimus concentRation/Dose Ratio over the first postoperative days in recipients of living-donor liver transplantation (LDLT). Genotyping assays were performed for the major 10 polymorphisms in the MDR1 gene by the polymerase chain reaction-restriction enzyme length polymorphism method. The allele frequencies of variations at five positions were almost comparable with those in the former studies in Caucasians and Japanese, but there was no variation at the other five positions. Although no polymorphism correlated with the intestinal expression of MDR1 mRNA or the tacrolimus concentRation/Dose Ratio in the LDLT recipients, the C3435T polymorphism significantly affected the intestinal expression level of CYP3A4 mRNA as follows; 3435C/C>3435C/T (P 3435T/T (P < 0.01 vs. 3435C/C). Therefore, the identified polymorphisms including C3435T in the MDR1 gene were indicated to have no influence on the intestinal expression level of Pgp or the tacrolimus concentRation/Dose Ratio in the recipients of LDLT. On the other hand, the C3435T polymorphism of MDR1 was suggested to correlate with the enterocyte expression of CYP3A4 rather than Pgp linking unknown genetic variation in CYP3A4 gene.

Dany Anglicheau - One of the best experts on this subject based on the ideXlab platform.

  • impact of cytochrome p450 3a5 genetic polymorphism on tacrolimus Doses and concentRation to Dose Ratio in renal transplant recipients
    Transplantation, 2003
    Co-Authors: Eric Thervet, Dany Anglicheau, Barry P King, Mariehelene Schlageter, Bruno Cassinat, Philippe Beaune, Christophe Legendre, Ann K Daly
    Abstract:

    Background Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. Methods CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus Dose and concentRation-to-Dose Ratio. Results The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean Doses required to obtain the targeted concentRation-to-Dose Ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. Conclusions Determination of CYP3A5 genotype is predictive of the Dose of tacrolimus in renal transplant recipients and may help to determine the initial daily Dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

  • association of the multidrug resistance 1 gene single nucleotide polymorphisms with the tacrolimus Dose requirements in renal transplant recipients
    Journal of The American Society of Nephrology, 2003
    Co-Authors: Dany Anglicheau, Mariehelene Schlageter, Bruno Cassinat, Philippe Beaune, Christophe Legendre, Celine Verstuyft, Pierre Laurentpuig, Laurent Becquemont, Eric Thervet
    Abstract:

    ABSTRACT. The immunosuppressive drug tacrolimus, whose pharmacokinetic characteristics display large interindividual variations, is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 ( MDR1 ) gene. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. Because P-gp is known to control tacrolimus intestinal absorption, it was postulated that these polymorphisms are associated with tacrolimus pharmacokinetic variations in renal transplant recipients. The objective of this study was to evaluate in a retrospective study of 81 renal transplant recipients the effect on tacrolimus dosages and concentRation/Dose Ratio of four frequent MDR1 SNP possibly associated with P-gp function (T-129C in exon 1b, 1236C>T in exon 12, 2677G>T,A in exon 21, and 3435C>T in exon 26). As in the general population, the SNP in exons 12, 21, and 26 were frequent (16, 17.3, and 22.2% for the variant homozygous genotype, respectively) and exhibited incomplete linkage disequilibrium. One month after tacrolimus introduction, exon 21 SNP correlated significantly with the daily tacrolimus Dose ( P ≤ 0.05) and the concentRation/Dose Ratio ( P ≤ 0.02). Tacrolimus Dose requirements were 40% higher in homozygous than wild-type patients for this SNP. The concentRation/Dose Ratio was 36% lower in the wild-type patients, suggesting that, for a given Dose, their tacrolimus blood concentRation is lower. Haplotype analysis substantiated these results and suggested that exons 26 and 21 SNP may be associated with tacrolimus Dose requirements. Genotype monitoring of the MDR1 gene reliably predicts the optimal Dose of tacrolimus in renal transplant recipients and may predict the initial daily Dose needed by individual patients to obtain adequate immunosuppression. E-mail: Dany.Anglicheau@biomedicale. univ-paris5.fr