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1.
S. C. Kabasakul M. Clarke H. Kane J. Karsten G. Clark 《Pediatric nephrology (Berlin, Germany)》1997,11(3):318-321
A major factor influencing whole blood cyclosporin A levels in young children with renal transplants is the variable absorption
of Sandimmun (SIM). Neoral (NEO) is a new microemulsion of cyclosporin A (CYA) that has been reported to have better absorption
characteristics. We compared the pharmacokinetics of SIM and NEO in nine renal transplant recipients aged less than 11 years
(range 4.8 – 10.9 years) and observed clinical parameters during 6 months of NEO therapy. Median CYA dosage was 149 mg/m2 per day (range 98 – 226). We observed an increase in the maximum CYA concentration (Cmax) of 114%, an increase in area under the curve (AUC) of 71% and the time to reach Cmax was reduced from 1.75 h to 1.25 h with NEO, while 12-h trough levels (C12 h) did not change significantly. AUC correlated
with C12 h for SIM (r
2 = 0.833) and NEO (r
2 = 0.699) and also C1.5 h for NEO (r
2 = 0.775). During 24 weeks’ follow-up, the coefficient of variation of CYA levels was lower for NEO (13%) than for SIM (20%).
Although CYA dosages at the start and the end of 6 months on NEO were similar, only one patient was maintained on a constant
dose. Four patients had acute reversible rises in plasma creatinine which responded to a 11% reduction in NEO dose; their
increase in AUC was greater than those patients not showing a rise in plasma creatinine. Overall, median plasma creatinine
was unchanged at the end of the study. NEO was well tolerated by the patients; temporary nausea and headache were experienced
by three patients and one of them stopped NEO after 20 days. Other biochemical parameters were not significantly different
on NEO.
Received May 28, 1996; received in revised form and accepted October 24, 1996 相似文献
2.
M. Winkler B. Ringe K. Oldhafer A. Kattner L. Färber A. Maibücher K. Wonigeit R. Pichlmayr 《Transplant international》1995,8(4):324-326
We analysed the absorption, after oral application, of a new galenic form of cyclosporin A (CyA-NOF) in liver-grafted patients (n=12) during the 1st week (days 2–4) after transplantation. Pharmacokinetic profiling was performed with an open or clamped T tube in situ or with the T tube absent. The pharmacokinetic parameters of CyA-NOF were influenced by T tube clamping and bile diversion. The highest AUC, Cmax and earliest Tmax values were found in patients without a T tube in situ, indicating that absorption of CyA-NOF in patients during the early course after liver transplantation is not bile-independent. CyA-NOF, at a dose of 7.5 mg/kg, was enterally absorbed with appropriate AUC and Cmax levels. Patients receiving a starting dose of 7.5 mg/kg were successfully maintained on CyA-NOF during the subsequent clinical course. 相似文献
3.
R. H. Moore 《Transplant international》1996,9(S1):S311-S313
Abstract The safety and tolerability of transferring maintained renal transplant patients from Sandim-mun to Neoral is being assessed in a multicentre, open-label, single-arm study. A total of 250 patients has been enrolled and results are available from 75 patients up to 12 months post-transfer. A slight trend to higher mean cyclosporin trough levels was seen in this cohort, but trough levels were unchanged in the sub-group receiving ± 1 dose changes. The mean dose fell by 13 %. Creatinine levels showed a slight overall upward trend. Blood pressure and uric acid were unchanged and adverse events were typical of those seen with Sandim-mun. Neoral was well-tolerated. Data from the full cohort of 250 patients up to 3 months post-transfer support these findings. These results indicate that transfer from Sandim-mun to Neoral is safe and well-tolerated and provides appropriate im-munosuppression at a lower average dose than Sandimmun. The Neoral dose should be adjusted promptly, as required, to maintain the target trough level. 相似文献
4.
E. A. Mueller J. M. Kovarik J. B. van Bree A.E. Lison K. Kutz E. A. Mueller J. M. Kovarik J. B. van Bree K. Kutz 《Transplant international》1994,7(S1):267-269
Abstract The steady-tate pharmacokinetics of a new oral formulation of cyclosporin A (Sandimmun Neoral, NOF, a microemulsion) was compared with those of the market formulation (Sandimmun, SIM) in stable renal transplant patients. Both formulations were administered as soft gelatin capsules every 12 h with doses adjusted to provide comparable trough concentrations ( C ss min). Whole blood samples were obtained over a steady-tate dosing interval (τ), and the cyclosporin A level was determined by a specific monoclonal RIA. Both formulations were well tolerated. The mean doses were 139 ± 27 mg (SIM) vs. 120 ± 19mg (NOF), indicating a milligram doseconversion factor of approximately 1:1 to yield comparable troughs. NOF exhibited a stronger correlation between AU C ss and C ss min ( r 2 = 0.821) compared with SIM ( r 2 = 0.288), due in part to less variability in the NOF profiles. Average increases of 39% in C ss max and 15% in AU C ss T during treatment with NOF were not associated with any safety concerns over the 4-week exposure to Sandimmun Neoral, as evidenced by the absence of changes in blood pressure, hematologic and biochemical parameters (including serum creatinine and blood urea nitrogen, BUN) and ultrasound of the transplanted kidney. 相似文献
5.
Timothy E. Bunchman Rulan S. Parekh Joseph T. Flynn William E. Smoyer David B. Kershaw Rudolph P. Valentini Brenda J. Pontillo Jill Sandvordenker Catherine Brown Aileen B. Sedman 《Pediatric nephrology (Berlin, Germany)》1998,12(1):2-5
Neoral was instituted in pediatric renal transplant patients with the hypothesis it would have more predictable kinetics than
Sandimmun. However, significant questions have arisen concerning potential toxicity and dosing interval related to its rapid
absorption with subsequent high initial peak. This is compounded by the fact that children appear to metabolize cyclosporine
at a greater rate than adults. This combination of a rapid peak and rapid absorption may then result in lower trough levels
at 12 h. We compared the trough cyclosporine levels of nine children who received Neoral with nine who received Sandimmun
at the time of initial transplantation. More frequent dosing (every 8 h) was required in the Neoral population compared with
the Sandimmun population for the 1st month in order to obtain comparable trough levels. Beyond the initial 4–6 weeks, trough
levels were similar for Neoral and Sandimmun. Whereas 1-month creatinine levels and blood pressures were similar, the number
of blood pressure medications was significantly higher in the Neoral group. At 5.5 ± 1.1 months’ followup, a single patient
in the current Neoral group and in the retrospective Sandimmun group each experienced a single OKT3 allograft-treated rejection.
We suggest that the area under the curve is different in Neoral than Sandimmun, and the initial dosing frequency may need
to be adjusted accordingly.
Received August 21, 1996; received in revised form June 27, 1997; accepted June 30, 1997 相似文献
6.
Rafael T. Krmar Elke Wuhl Reinhard Ding Michael Aulmann Karl Schärer 《Transplant international》1996,9(5):476-480
Pharmacokinetics of the new galenic formulation of cyclosporin A, Neoral, (Sandoz) was examined in 12 stable young patients after renal transplantation. Six of these patients were tested before and 4 weeks after switching from the standard formulation Sandimmun to Neoral. No significant changes were observed in trough levels, tmax, Cmax, and AUC0–12h, but the absorption rate constant (Ka) increased (P=0.003). Glomerular filtration rate, as assessed by inulin clearance, increased by more than 10% in three patients and decreased in two, and was usually associated with a respective drop and rise in Cmax and AUC0–12h of cyclosporin A. The large interindividual variability in the response to the conversion to the new formulation points to a need for close monitoring of cyclosporin A trough levels and renal function after switching from Sandimmun to Neoral in this age group in order to avoid nephrotoxicity. 相似文献
7.
Ferda M. Şenel Sedat Yildirim Hamdi Karakayali Gökhan Moray M. Haberal 《Transplant international》1997,10(5):357-361
We compared the mean trough level/dose (L/D) ratio, mean coefficient of variation (CV) of individual patients, and graft,
patient, and rejection-free survival rates of 40 renal transplant recipients receiving Neoral (CyE) with 103 consecutive renal
transplant recipients receiving Sandimmun (CyA). The mean L/D ratio on the 3rd post-transplant day (16.2 vs 11.8, P < 0.04), in the 1st week (24.6 vs 16.1; P < 0.03), and 1st month (39.1 vs 28.7; P < 0.05) were higher in the CyE group. In both groups the L/D ratio improved in proportion to the duration of time post-transplant
and reached a maximum in the 3rd post-transplant month. In the early post-transplant period in particular, the number of patients
achieving target levels was significantly higher, and the mean dose needed to achieve target levels lower, in the CyE group.
The variation in trough levels, demonstrated by the CV, was lower in the CyE group (0.41 ± 0.14) than in the CyA group (0.62
± 0.21; P < 0.005). Actuarial 1-year patient and graft survival rates in the CyE group were 100 % and 96 %, respectively; these were
similar to the 100 % and 95 % in the CyA group. The 1-year rejection-free survival rate in the CyE group was 61 % compared
to 43 % in the CyA group (P < 0.02). We conclude that it is possible to obtain higher blood trough levels at lower doses by administering CyE, particularly
in the early post-transplant period. The lower variability of trough levels and the higher L/D ratio in the CyE group, which
are related to improved bioavailability of CyE, may explain the lower rejection rate among these patients. In this study,
the microemulsion formulation of cyclosporin (CyE) was found to be more beneficial and cost-effective as induction and maintenance
immunosuppression than the conventional formulation (CyA).
Received: 28 January 1997 Received after revision: 13 May 1997 Accepted: 15 May 1997 相似文献
8.
Effect of grapefruit juice on Sandimmun Neoral absorption among stable renal allograft recipients. 总被引:4,自引:0,他引:4
C Bistrup F T Nielsen U E Jeppesen H Dieperink 《Nephrology, dialysis, transplantation》2001,16(2):373-377
BACKGROUND: The oral formulation of cyclosporin A (CsA)-Sandimmun-has a highly variable absorption. The development of a CsA microemulsion-Sandimmun Neoral-resulted in increased bioavailability, and decreased variability of absorption. The first oral formulation (Sandimmun) interacted with numerous other drugs and grapefruit juice. Several of these interactions might be explained by decreased pre-systemic metabolism by a cytochrome-enzyme (e.g. CYP3A4) located in the enteral mucosa, and/or via the P-glycoprotein-mediated decreased transport of CsA back from enterocytes into the gut lumen. The purpose of this pharmacokinetic study was to investigate the interaction between Sandimmun Neoral and grapefruit juice. METHOD: Eight stable renal transplant recipients were studied during two 8-h sessions in a randomized cross-over design with 4 weeks interval. Following an overnight fast the patients ingested their habitual morning dose of Neoral either with water or with grapefruit juice. During the 8-h study period 10 blood samples were taken for determination of CsA concentration. These results formed the basis for calculation of area under curve (AUC), and half-life (t(1/2)). Maximum concentration (C(max)) and time until C(max) (t(max)) were obtained from the concentration-time profile. RESULTS: The median AUC increased by 38% (12-194%) (P<0.05) following co-administration of Neoral with grapefruit juice. There were no significant changes in C(max), t(max), and t((1/2)). CONCLUSION: Co-administration of Sandimmun Neoral with grapefruit juice resulted in an increased bioavailability of CsA, indicating unchanged pre-systemic enterocyte first-pass metabolism as compared to Sandimmun. There was no impact of an oral grapefruit juice load on systemic clearance of CsA. It seems prudent to advise renal allograft recipients treated with Sandimmun Neoral not to ingest their medication with grapefruit juice. 相似文献
9.
A. J. Hoitsma 《Transplant international》1996,9(S1):S314-S317
Abstract A double-blind switchover study was carried out on 70 renal transplant patients to assess the value of a new cyclosporin derivative, IMM 125. Preclinical in vitro and in vivo studies indicated that IMM 125 was as equally immunosuppressive as Sandimmun, but that its therapeutic index should be superior. The duration of the treatment was 24 weeks. The assumption that the dosage of IMM 125 could be 2.5 times lower than Sandimmun proved to be false; three patients suffered acute rejection episodes, probably as a consequence of the low dosage, and dosage adjustments had to be made for all patients receiving IMM 125 after only a few weeks. Although IMM 125 is an effective immunosuppressive agent, it does not appear to offer advantages over Sandimmun with regard to renal function. In addition, IMM 125 causes some disturbances in liver function. 相似文献
10.
环孢素新剂型Neoral在肾移植中的应用 总被引:1,自引:0,他引:1
对10例肾移植患者作山地明转换Neoral试验进行药效动力学对比研究,30例新移植患者应用Neoral进行临床观察。结果表明,Neoral最高血浓度(Cmax)较山地明高282±84ng/ml,达峰时间(Tmax)短0.79±0.29h,CSA暴露(AUC)大1533±169ng/(h·ml)(P<0.05)。提示Neoral有较好地抗排斥反应作用,但由于吸收迅速,血药浓度易超过治疗窗水平而引起毒副反应。本组肝中毒达20%。认为Neoral与山地明转换比例应为1:0.8~1:0.9,以避免毒副作用发生;Neoral服药量可较山地明常规剂量减少25%。 相似文献
11.
Reduced variability of Neoral pharmacokinetic studies in pediatric renal transplantation 总被引:1,自引:0,他引:1
Meier-Kriesche HU Swinford R Kahan BD Brannan P Portman RJ 《Pediatric nephrology (Berlin, Germany)》2000,15(1-2):2-6
In adult renal transplant recipients the Neoral area under the curve (AUC) displays less inter- and intra- individual variability
than Sandimmune, and those renal transplant recipients with reduced intra-individual variability of the AUC have a lower risk
for chronic rejection. As variability of Neoral pharmacokinetic (Pk) parameters has not been investigated in pediatric renal
transplant recipients, we retrospectively analyzed 453 Pk profiles in 14 pediatric patients who were switched from Sandimmune
to Neoral and compared the inter- and intra-individual variability of the Pk profiles on both formulations. After the switch,
we observed less inter- and intra-individual variability of AUC, the 2-h concentration, and the oral clearance. As clearance
with both formulations is supposedly equal, the significantly lower intra-individual variability of oral clearance is most
likely an effect of less variable absorption. While the lower inter-individual variability of the Pk parameters suggests increased
success in keeping cyclosporine concentrations on target, the lower intra-individual variability leads to the hypothesis that
with Neoral, a lower incidence of chronic rejection might be achieved.
Received: 8 February 2000 / Revised: 17 May 2000 / Accepted: 22 May 2000 相似文献
12.
S. Ohlman A. Lindholm H. Gbel H. Wilczek G. Tydn F. Reinholt J. Swe C.-G. Groth 《Transplant international》1992,5(Z1):S464-S469
Animal studies have suggested that the analogue cyclosporin G (CyG) may be less nephrotoxic than cyclosporin A (CyA). A pilot study was therefore performed in 10 primary cadaveric renal allograft recipients who were randomized to receive posttransplant immuno-suppression with either CyA or CyG. The follow-up time was a minimum of 1 year. One graft was lost in each group. All patients in both groups experienced at least one acute rejection episode. Episodes of acute nephrotoxicity were observed in both groups. Renal function, as assessed by determinations of the serum creatinine level and chromium-ethylene diamine tetra-acetic acid (Cr-EDTA) clearance, did not differ between the two groups. Renal allograft biopsies showed a significantly higher degree of fibrosis in the CyG group than in the CyA group. All CyG-treated patients evidenced laboratory signs of acute liver toxicity, which was dose-dependent and reversible. Today, all CyG-treated patients have been switched to CyA. This study shows that immunosuppression after renal transplantation in man is possible with CyG; however, it does not seem to have any advantages over CyA. 相似文献
13.
Reversible renal failure in renal transplant patients receiving oral acyclovir prophylaxis 总被引:1,自引:0,他引:1
Tariq Ahmad Martin Simmonds Angus G. McIver Mary E. McGraw 《Pediatric nephrology (Berlin, Germany)》1994,8(4):489-491
Two children who developed acute renal failure in the immediate post-renal transplantation period are presented. Each was immunosuppressed with cyclosporin and was also receiving oral acyclovir for prophylaxis against cytomegalovirus infection. Renal biopsy findings suggested drug toxicity. Discontinuation of acyclovir coincided with reversal of renal impairment. As cyclosporin levels were at the lower end of the therapeutic range, we believe acyclovir to be the likely causative agent. 相似文献
14.
John M. Kovarik Zoltan Kallay Edgar A. Mueller Johannes B. van Bree Wolfgang Arns Eckhard Renner 《Transplant international》1995,8(5):335-339
Potential differences in the acute effect of cyclosporin on renal function when dosed orally as the current market formulation or following a milligram-to-milligram conversion to a new microemulsion formulation were investigated in 14 stable kidney transplant patients. The study consisted of three sequential periods of 2 weeks duration each. Patients entered (period I) and completed (period III) the investigation with the market formulation and received the microemulsion formulation in period II; individualized cyclosporin doses remained unchanged throughout the study. Over one steady-state dosing interval at the end of each study period, whole blood cyclosprin pharmacokinetic profiles were assessed in parallel with endogenous creatinine clearances over sequential 1-to 2-h intervals. The rate and extent of cyclosporin absorption were significantly greater (P<0.01) from the microemulsion formulation with average increases of 73% in peak concentration and 44% in area under the curve compared to the market formulation. Sequential creatinine clearances exhibited a transient decrease with the nadir occurring on average between 4 and 6h post dose followed by a rapid return to baseline. Specifically in period I on the market formulation, clearances decreased from a baseline of 71.7±20.6 to a minimum of 51.1±17.9 ml/min per 1.73 m2 (similar values in period III) and from 76.8±24.8 to 53.5±17.5 ml/min per 1.73 m2 in period II on the microemulsion. Neither the baseline nor minimum clearances were significantly different among the study periods. Hence, the pharmacokinetic differences between the formulations did not acutely influence the pattern of glomerular filtration rate following the initial milligramto-milligram changeover in stable renal transplant patients. 相似文献
15.
G. Morris-Stiff D. Talbot V. Balaji K. Baboolal K. Callanan J. Hails R. Moore D. Manas R. Lord W.A. Jurewicz 《Transplant international》1998,11(S1):S98-S99
Abstract Five patients with cyclosporin-related haemolytic uraemic syndrome (HUS) following cadaveric renal transplantation were converted from cyclosporin- to ta-crolimus-based immunosuppression. All patients had biochemical, haematological and biopsy evidence of HUS at the time of conversion. Four of the patients showed complete resolution of the syndrome within 1 week of conversion with normalisation of haemoglobin, platelets and lactate dehydrogenase levels. In the fifth patient renal function stabilised with slow resolution of the haematological and biochemical parameters. Four of the five patients are still taking tacrolimus, one having converted back to cyclosporin due to marked hair loss. We conclude that conversion to tacrolimus appears to be an effective treatment for cyclosporin-related HUS following renal transplantation. 相似文献
16.
H. Jiang Shozo Sakuma Yasutomo Fujii Yuka Akiyama Toshikazu Ogawa Kouichi Tamura Masakazu Kobayashi Takashi Fujitsu 《Transplant international》1999,12(2):92-99
Although tacrolimus has been studied in a wide variety of experimental animal models, we are the first group to systematically
study the effect of tacrolimus on rat renal allograft survival, as primary therapy and as anti-rejection therapy, in comparison
with cyclosporin A (CyA). Renal grafts were transplanted from BN to LEW rats. Tacrolimus and CyA were administrated orally
from day 0 for 50 days as primary therapy after grafting. Allografts were rejected after a median survival time (MST) of 8
days. Both tacrolimus und CyA significantly prolonged renal allograft survival, in a dose-dependent manner compared with the
allograft controls. The most effective dose was 3.2 mg/kg, per day for tacrolimus, and 10 mg/kg per day for CyA. There was
no significant difference in renal function between the group treated with the most effective dose of tacrolimus and the CyA-treated
group. The percentage of detectable serum IL-2 level was 45 % in the allograft control group, but was undetectable in groups
treated with the most effective dose of tacrolimus or CyA at days 3 and 6 after grafting. On the other hand, no side effects
were noted in recipient rats by daily inspection, body weight change, and histological studies, although minimal tubular vacuolation
was encountered in the group treated with CyA 32 mg/kg per day. In addition, the most effective doses of tacrolimus and CyA
were studied as anti-rejection therapy. All of the 5 recipients treated with tacrolimus from days 2–14, and 3 of the 5 treated
from days 4–16 after grafting, survived for more than 50 days. However, the MST was 19 days for recipients treated with CyA
from days 2–14, and 13 days for those treated from days 4–16 after grafting. In summary, tacrolimus as primary therapy induced
rat renal allograft survival with renal function and side effects comparable with those of CyA. Interestingly, when both agents
were used as anti-rejection therapy, tacrolimus, but not CyA, could significantly overcome ongoing renal allograft rejection
in the rat.
Received: 31 March 1998 Received after revision: 9 September 1998 Accepted: 12 October 1998 相似文献
17.
Neumayer H.-H.; Farber L.; Haller P.; Kohnen R.; Maibucher A.; Schuster A.; Vollmar J.; Budde K.; Waiser J.; Luft F. C. 《Nephrology, dialysis, transplantation》1996,11(1):165-172
BACKGROUND: A new galenic form of cyciosporin A has been developed, basedon microemulsion technology. The bioavailability of the compoundis reiativeiy independent of food intake and bile flow. It wasthe purpose of this prospective clinical trial to study thesafety of the microemulsion form of cyclosporin A. METHODS: Three hundred and two renal transplant patients, stratifiedaccording to transplant age, were switched from the conventionalto the new micro-emulsion formulation of cyclosporin A. A 1:1conversion ratio was used. Measurements included CsA levels,S-creatinine, liver enzymes, uric acid, and blood pressure.Measurements were performed at baseline and on days 4, 8, 15,29 and months 3, 6 and 12 after conversion. Dose adjustmentswere performed to achieve trough levels of 80120 ng/ml. RESULTS: Within the 12-month observation period the cyclosporin dosewas reduced by 14.7% (from 204±60 mg/day at baselineto 174±51 mg/day after conversion, P<0.001). Acutely,i.e. by day 8, a 1:1 dose conversion resulted in a modest increaseof mean drug trough levels (from 114 ng/ml at baseline to 120ng/ml, P<0.01). This increase was accompanied by an increasein serum creatinine concentration, a decrease in calculatedcreatinine clearance, and an increase in uric acid values (P0.05).Liver enzymes remained unchanged while systolic and mean arterialblood pressure decreased (P<0.05). After 1 month, drug troughlevels had decreased to baseline (112 ng/ml) and remained thereuntil month 6. They were significantly lower after 12 months(102±33 ng/ml, P<0.001). Creatinine clearance valuesincreased to above baseline at 6 and 12 months. Within the 1-yearperiod there occurred 24 (=8%) episodes of biopsy-proven rejectionand seven episodes of cyclosporin-attributed nephrotoxicity. CONCLUSIONS: The 1:1 conversion from conventional cyclosporin A to the microemulsionformulation is efficacious and safe, but an initial dose reductionof 10% is advised in patients with trough levels in the high-normalrange. 相似文献
18.
Pharmacokinetics of cyclosporine in pediatric long-term liver transplant recipients converted from Sandimmun to Neoral 总被引:1,自引:0,他引:1
M. Melter Burkhard Rodeck Rüdiger Kardorff Peter F. Hoyer Johannes Brodehl 《Transplant international》1997,10(6):419-425
Absorption of cyclosporin from the microemulsion formulation Neoral is less variable than from Sandimmun. Because of a lack
of data in pediatric liver transplant recipients, the pharmacokinetic profiles with Sandimmun and Neoral were compared in
a conversion study. Thirty-eight children with stable graft function were converted 2–12.3 years post-transplant at a 1:1
ratio. The trough-level (Cmin) with Neoral was 123 ± 39 ng/ml versus 134 ± 29 ng/ml with Sandimmun (P = NS), the area under the time-concentration curve (AUC) was 3325 ± 1125 ng*h/ml versus 2423 ± 846 ng*h/ml (P < 0.001), the peak concentration (Cmax) was 650 ± 280 ng/ml versus 337 ± 142 ng/ml (P < 0.001), and the median time to Cmax was 2 h (range 0.5–3 h) versus 4 h (range 1–8 h; P < 0.05). The weak correlation between Cmin and AUC with Sandimmun (r = 0.5; P = NS) was improved by using Neoral (r = 0.7; P < 0.001). The best predictor of AUC was the 2-h concentration (C2 h) of Neoral (r = 0.9; P < 0.001). Increased absorption and a more predictable pharmacokinetic profile with Neoral permit safer therapeutic monitoring
in children. The exclusive measurement of Neoral-C2 h allows one to estimate drug exposure with high precision ( > 90 %).
Received: 12 February 1997 Received after revision: 16 May 1997 Accepted: 5 June 1997 相似文献
19.
Didier Ducloux Pierre-Louis Carron Gerard Motte Abdelfatah Ab Jean-Michel Rebibou Catherine Bresson-Vautrin Pierre Tiberghien Yves Saint-Hillier Jean-Marc Chalopin 《Transplant international》2002,15(8):393-396
Renal transplant recipients have a well-recognized increased risk of de novo neoplasia. In this study, we investigated whether lymphocyte subset count could predict the risk of developing noncutaneous neoplasia (NCSC) in renal transplant recipients (RTR). Between January 1995 and December 1995, lymphocyte subsets (CD4, CD8, CD19) were measured in 281 RTR. This population was studied until November 1999 for the development of NCSC. The mean follow-up was 42+/-9 months. Neoplasm was diagnosed in 22 patients (7.9%). Patients who developed a cancer were significantly older (53.8+/-6 years vs 38+/-16 years, P<0.0001), had lower CD4 (234+/-126/mm(3) vs 543+/-214/mm(3), P<0.005) and CD19 (19+/-9/mm(3) vs 51+/-22/mm(3), P<0.0001) levels, and more frequently had past histories of skin cancer (24% vs 4%, P<0.01). Cox regression revealed that high CD4 levels (RR 0.73, 95% CI 0.62-0.89 for each 100/mm(3) increase in CD4 cell count) were associated with decreased risk of NCSC, whereas age (RR 2.49, 95% CI 1.12-5.92 for each 10-year increase in age) was predictive of the subsequent development of NCSC. To conclude, CD4 cell depletion is associated with the development of solid cancers and lymphoma in RTR. 相似文献
20.
P. E. Wallemacq Raymond Reding Etienne M. Sokal Jean Ville de Goyet Stéphane Clement de Clety Véronique Van Leeuw Marc De Backer Jean-Bernard Otte 《Transplant international》1997,10(6):466-470
Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability
of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces
better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a
complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic
profiles were set up with data obtained from tests taken during i. v. administration of CyA, after the first oral NEO dose,
and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively,
and the bioavailabilities were 22 % and 21 % for the first and last NEO doses. A large interpatient variability was observed.
This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability
of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both
NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of
adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.
Received: 29 November 1996 Received after revision: 10 April 1997 Accepted: 15 May 1997 相似文献