Metandienone Wikipedia

**Introduction**

The oral formulation of *tacrolimus* (marketed under the trade name **Prograf®**) is a macrolide immunosuppressant that has been extensively used in solid‑organ transplantation, notably kidney, heart and liver transplants. The drug was first isolated from *Streptomyces tsukubaensis* (formerly *S.* rhodospora) and entered clinical practice in the early 1990s after demonstrating its potent ability to inhibit T‑cell activation and proliferation.

**Mechanism of action**

Tacrolimus is a potent inhibitor of calcineurin, a phosphatase that activates the nuclear factor of activated T cells (NFAT). By forming a complex with FK506‑binding protein 12 (FKBP‑12), tacrolimus blocks dephosphorylation of NFAT, preventing its translocation into the nucleus and thereby suppressing interleukin‑2 production. The drug’s high affinity for FKBP‑12 (~10^−8 M) accounts for its potency at low concentrations.

**Pharmacokinetics**

- **Absorption** – Oral tacrolimus is poorly absorbed (bioavailability ~25%) but highly variable due to food, gastric pH, and drug interactions.
- **Distribution** – Extensive binding to erythrocytes (~90 % of plasma concentration) and high protein binding (>99 %).
- **Metabolism** – Primarily hepatic CYP3A4 and CYP3A5; the major metabolite is tacrolimus N‑oxide.
- **Elimination** – Renal excretion accounts for ~20 % of clearance; the rest is biliary.
- **Half‑life** – 12–18 h in adults, shorter in children due to higher hepatic clearance.

The therapeutic range (C0) is typically 5–15 ng/mL for solid organ transplantation; levels outside this window risk rejection or toxicity. Because of the narrow margin and high inter‑individual variability, close monitoring with TDM is essential.

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### 3. Clinical Utility of a Point‑of‑Care Tacrolimus Assay

#### 3.1 Advantages Over Conventional Immunoassays

| Feature | Conventional Immunoassay (ELISA/CLIA) | POC Flow‑Based Fluorescence Assay |
|---------|---------------------------------------|-----------------------------------|
| Sample type | Serum/plasma; requires venipuncture and centrifugation | Capillary whole blood via fingerstick |
| Turn‑around time | 2–4 h (batch processing) | 95% sensitivity, >90% specificity for detecting acute myocardial injury.
- **Turn‑Around Time (TAT)**: ≤15 min from sample receipt to result display.
- **Positive Predictive Value (PPV) / Negative Predictive Value (NPV)**: Monitor PPV/NPV across patient prevalence strata.
- **Error Rate**: 99th percentile); high‑risk presentation per GRACE score >140. |
| **Exclusion Criteria** | • Known coronary artery disease (≥50 % stenosis)
• Contraindication to MRI (claustrophobia, non‑MRI compatible implants)
• Severe renal dysfunction (eGFR