Correlation between Cyclosporine Blood Levels and Area under Blood Concentration Time Curve in Iraqi Bone Marrow Transplant Patients Treated with Neoral® Oral Solution

Abstract

Cyclosporine is a potent immunosuppressive drug. It has a narrow therapeutic index, and therefore the measurement of cyclosporine’s blood concentration is essential to obtain optimal therapy. Measurement of the area under the blood concentration-time curve (AUC) is reflective of total drug exposure. However, for organ transplant patients, the measurement of AUC involves many problems and difficulties. Thus, it is more clinically acceptable to use a single blood sample as a surrogate index of total drug exposure. Fifty-four adults bone marrow transplant Iraqi patients were given cyclosporine every 12 h as prophylaxis using Neoral® oral solution. Steady-state blood concentrations were monitored for each patient at zero time and then at 1, 2, 3, 4, 6, 8, 10, and at 12 h post-dosing. Cyclosporine blood levels were determined by using AXSYM automated immuno-analyzer which is a fluorescence polarization immunoassay (FPIA). The present investigation demonstrated the best correlation between C2 and the corresponding AUC0–4h and AUC0–12h compared to other concentrations. After two months of cyclosporine therapy, no unexpected biochemical changes and adverse effects were registered. It is concluded from this study that a single blood sample obtained at 2 h post-dosing (C2) and possibly at 3 h post dosing (C3) are ideal surrogate indexes for reflecting total drug exposure, and therefore may be used in clinical practice for predicting therapeutic and toxic effects of cyclosporine.

Evaluation of Vitamin D3-Conjugated Selenium Nanoparticles (Se-NPs) on White Blood Cells, Liver, and Kidney Functions in Induced Immunosuppressed Rats

“…The results agreed with what was reached by [19] who indicated a significant increase in the indicators of ALT, AST and ALP when dosed with cyclosporine (CsA) for male laboratory rats, as the researchers showed that hepatotoxicity induced by CsA begins with the imbalance of arachidonic acid and the synthesis of eicosanoids and the release of free radicals, especially hydroxyl radicals that begin In lipid oxidation and secondary activation of physiological antioxidant defenses. It also agreed with the results of [20] who found that cyclosporine caused a significant increase in the levels of AST, ALT and ALP enzymes in blood samples of 54 Iraqi patients. The results agreed with the findings of [21], [22] and [23] that treatment with selenium nanoparticles (Se-NPs) caused a decrease in the values of AST, ALT and ALP enzymes in infected male laboratory rats, which is an indication of inhibition of inflammation and protection of the liver in Infected mice [23] stated that Se-NPs improve STZ dysfunction through its radical scavenging activity, besides its safety and liver tissue function resulting from the role of Se-NPs in treating liver dysfunction and thus lowering the levels of high values of the enzymes AST, ALT and ALP.…”

Stimulatory Effect of CMV Immunoglobulin on Innate Immunity and on the Immunogenicity of CMV Antigens

“…The stimulatory effects of CMVIG, CMV lysate, and CMVIG-opsonized CMV lysate were observed at low concentrations of cyclosporine A (Figure 7 ) and tacrolimus (Figure S4, SDC, http://links.lww.com/TXD/A374 ) and were comparably inhibited by higher concentrations of calcineurin inhibitors (Figures 7 and Figure S4, SDC, http://links.lww.com/TXD/A374 ). Of note, the target blood level of cyclosporine A in transplant recipients usually ranges from 100 to 800 ng/mL, 58 - 61 which corresponds to molar concentrations ranging from 0.083 to 0.664 μM. This precisely corresponds to the range of cyclosporine A concentrations showing weak to strong inhibition of PBMC response in our ELISpot assay (Figure 7 ).…”

“…com/TXD/A374) and were comparably inhibited by higher concentrations of calcineurin inhibitors (Figures 7 and Figure S4, SDC, http://links.lww.com/TXD/A374). Of note, the target blood level of cyclosporine A in transplant recipients usually ranges from 100 to 800 ng/mL, [58][59][60][61] concentrations showing weak to strong inhibition of PBMC response in our ELISpot assay (Figure 7).…”

Pharmacokinetics of Fluconazole tablets administered to healthy subjects ‎

“…Fluconazole was also prescribed recently for patients with diabetes mellitus [10]. Interestingly, fluconazole possesses unique and distinguished pharmacokinetic characteristics [3,4,11] in comparison to many other widely used drugs such as azithromycin [12], betahistine [13], doxazocin [14], cefixime [15], cyclosporine [16], amlodipine, valsartan, and hydrochlorothiazide [17]. There is a close similarity in the fluconazole's pharmacokinetics after intravenous, oral tablets, and oral suspension.…”

“…On the other extreme, If the given dose of the antimicrobial agent yields plasma levels above the maximum therapeutic levels, consequently drug therapy will be associated with adverse effect(s) which lead to stopping the drug usage, and replacement by other antimicrobial, or using a combination of antimicrobial agents which have many negative sides in term of the health and cost to the patient [12,15,[18][19][20]. Therefore, many pharmacokinetics, bioavailability, and bioequivalence researches were conducted in different countries and for almost all drugs to know the pharmacokinetic behaviors of the drug in each nation [12][13][14][15][16][17][18][21][22][23][24][25][26][27][28][29]. Among the researches conducted for fluconazole in particular, were for Thai [21], Arabic [18,22,23], Brazilian [24], Spanish [25], Serbian [26], Mexican [27], Bangladeshi [28], and Chinese individuals [29].…”