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Biomedical subjects

A Stephan

Publications and source records attributed to A Stephan.

At least 19 recordsLinked to original sources
PubMed2005

Switchability of neoral and equoral according to Food and Drug Administration rules and regulations.

According to the US Food and Drug Administration (FDA), if a drug product contains a drug substance that is chemically identical and is delivered to the site of action at the same rate and extent as another drug product, then it is equivalent and can be substituted (switchable) for that drug product. Methods used to define bioequivalence as stated by the FDA rules (FDA 21 CFR 320, 24) are (1) pharmacokinetic (PK) studies in healthy volunteers, (2) comparative clinical trials, and (3) pharmacodynamic (PD) studies (bioactivity). We evaluated the switchability of Equoral (IVAX-USA) with Neoral (Novartis Switzerland using all FDA rules. In a single oral dose, we undertook a comparative bioavailability study of Equoral (IVAX, USA) Neoral (Novartis, USA), and Neoral (Novartis UK). The pharmacokinetics of Equoral and Neoral were determined with blood levels at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16, 24, 30, 36, 42, and 48 hours. The area under curve (AUC), AUC extrapolated to infinity (AUC0-inf), rate of absorption (Tmax), extent of absorption (Cmax), half time (t1/2) of Equoral and Neoral were all within the 90% confidence interval of 80% to 125% boundaries. A comparative multinational multicenter clinical trial in stable renal transplant patients included 70 patients (22 women and 48 men) of mean age of 33 years (range, 26 to 43) was performed in Turkey, Lebanon, and Pakistan. In this study the ratios of LSM and the 90% confidence intervals for the Nontransformed/Parameters (AUC0-t, AUCinf, Tmax, and Cmax) of Equoral and Neoral SGC were 98% and 95%, respectively, which are within the 80% to 125% FDA acceptance range. For immunosuppressive drugs, the site of action is the lymphocyte and the measurable response is the decrease in lymphocyte count caused by the relative concentration of the drug in the lymphocyte. In a controlled switch, fixed-dose study, both Equoral and Neoral achieved the same concentration in the lymphocytes and caused the same degree of lymphocyte count reduction. The results of the testing (bioavailability-bioequivalence, clinical studies, and pharmacodynamic-bioactivity) required by FDA for interchangeability ("switchability") of immunosuppressive agents suggests that Neoral and Equoral are switchable.

Adult↗
PubMed2005

A transplanted kidney surviving total vessel occlusion and anuria.

We report a case of a 46-year-old white male with renal graft artery stenosis who developed acute renal shutdown with total anuria while on the ACE inhibitor lisinopril, one week following the discontinuation of aspirin. The serum creatinine was 8.5 mg/dl. Doppler ultrasound and MAG3 scintigraphy of the grafted kidney were highly suggestive of a viable but nonfunctioning kidney. A femoro-femoral bypass for total thrombosis of the right common iliac artery was performed distal to the occlusion. Immediate diuresis was obtained after establishing the bypass. Serum creatinine dropped to 1.35 mg/dl three days later. In this case we believe that the collateral circulation played a significant role in immediate recovery of kidney function by maintaining renal perfusion pressure and preventing acute tubular necrosis (ATN). We also believe that the ACE inhibitor might have contributed to salvaging the kidney by improving medullary oxygen balance and maintaining adequate medullary blood flow.

Anuria↗
PubMed2005

Mycophenolic acid plasma trough level: correlation with clinical outcome.

OBJECTIVES: Assess the relationship between clinical diagnosis, state of immunosuppression, mycophenolic acid (MPA) plasma trough levels (MPACmin), and mycophenolate mofetil (MMF) dosage in renal transplant recipients. MATERIALS AND METHODS: MPACmin were determined in 30 kidney transplant patients, of whom 7 exhibited biopsy-proven acute rejection. The remaining 23 had normal graft function. Graft outcome, defined by clinical diagnosis and serum creatinine level, was compared according to MPACmin, MMF dosage, and total lymphocyte count (LC). RESULTS: Patients with acute rejection had similar MPACmin (2.4 +/- 1.7 microg/mL), MMF dosages (1.7 +/- 0.5 g), and LCs (0.001165 +/- 0.0040 x 10(9)/L) when compared with normal patients (2.2 +/- 0.7 microg/mL, 1.7 +/- 0.4 g and 0.001160 +/- 0.00527 x 10(9)/L) respectively. Rejection rates were comparable irrespective of MPACmin)ranges and higher in those receiving the 1-g dose (30%) when compared with those receiving 1.5-g and 2-g doses (12.5% and 11.7%). No relationship was observed between MPACmin and MMF doses, and neither parameter correlated with LC. CONCLUSIONS: These results suggest that MPACmin is a poor correlate of clinical outcome and state of immunosuppression. Although the usually recommended dosage of MMF (2 g) may be associated with acute rejection, low-dose MMF (1 g) seems to constitute a higher risk.

Adult↗
PubMed2003

Consanguinity-associated kidney diseases in Lebanon: an epidemiological study.

Consanguineous marriages are common in many countries of the Middle East including Lebanon. Their impact on the repartition of kidney diseases and on the risk for familial nephritis is not known. We surveyed all of the dialysis centers in Lebanon. Nine hundred and twenty-five (925) patients and their private physicians were asked to answer a questionnaire. More than half of the hemodialysis (HD) patients had an unknown etiology of their kidney disease. Diabetes, polycystic kidney disease (PKD), chronic pyelonephritis and nephrosclerosis (NS) were the most commonly documented diagnoses. Consanguinity was present in 26% of the total HD population. More consanguineous patients with unknown renal etiology were diagnosed with their kidney diseases and initiated on dialysis before the age of 30 when compared with their non-consanguineous counter-parts (45% versus 33%, P<0.02 and 42% versus 27%, P<0.01), respectively. Similarly, consanguineous polycystic patients were diagnosed and started earlier on dialysis when compared with the non-consanguineous population (34% versus 12%, P<0.05 and 28% versus 8%, P<0.05), respectively suggesting a different disease pattern. Furthermore, the risk for family history of kidney disease was noticeable in the non-consanguineous population and significantly higher among the consanguineous patients (12% versus 18%, P<0.04). Consanguinity-associated kidney diseases affected all religious communities, in particular the Muslim and the Druze (36 and 39%), respectively versus 17% of the Christian community. Certain geographical areas were more involved than others such as the North, South and the Bekaa with the highest percentage (40%) in the latter. Socio-economical level was not a contributing factor. We conclude that the documentation of the underlying etiology in end-stage renal diseases (ESRD) seems to be deficient. Furthermore, consanguinity is prevalent in the Lebanese dialysis patients population, in particular the Muslim and the Druze communities. Consanguinity-associated kidney diseases pattern seems to differ from that of the general HD population by disease diagnosis and initiation at a younger age and a significantly higher risk for familial renal disease. It is a cultural phenomenon prevalent predominantly in the rural areas. We recommend a multi-approach including educational, informative and probably legislative strategy in order to limit and hopefully discourage consanguineous marriages.

Adult↗
PubMed2002

Nocturnal accumulation of cyclic 3',5'-guanosine monophosphate (cGMP) in the chick pineal organ is dependent on activation of guanylyl cyclase-B.

The role of cGMP in the avian pineal is not well understood. Although the light-sensitive secretion of melatonin is a well-known output of the circadian oscillator, pharmacologically elevated cGMP levels do not result in altered melatonin secretory amplitude or phase. This suggests that pineal cGMP signalling does not couple the endogenous circadian oscillator to the expression of melatonin rhythms. Nonetheless, the free-running rhythm of cGMP signalling implies a link to the circadian oscillator in chick pinealocytes. As the circadian rhythm of cGMP levels in vitro is not altered by pharmacological inhibition of phosphodiesterase activity, we infer that the synthesis, rather than the degradation of cGMP, is under circadian control. In vitro experiments with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine as well as with an inhibitor of the NO-sensitive soluble guanylyl cyclase (sGC), showed that the NOS-sGC pathway does not play a major role in the circadian control of cGMP generation. In organ culture experiments, we demonstrated that C-type natriuretic peptide (CNP), but not atrial natriuretic peptide (ANP), elevated daytime levels of cGMP. As CNP acts on the membrane guanylyl cyclase isoform B (GC-B), which is expressed at very high levels in mammalian pineals, we investigated the effect of the membrane GC-specific inhibitor HS-142 on chick pineal cGMP levels. CNP-induced daytime cGMP levels were reduced by HS-142. More importantly, 'spontaneously' high nocturnal levels of cGMP in vitro were reduced to daytime levels by acute addition of HS-142. These data implicate endogenous nocturnal CNP release and subsequent activation of GC-B as the major input driving cGMP synthesis in the chick pineal organ.

Animals↗