⚕ Clinical Pharmacokinetics
TDM Calculator
Therapeutic Drug Monitoring tools for clinical pharmacists. Select a module to begin.
CrCl / IBW
Cockcroft-Gault creatinine clearance, ideal & adjusted body weight
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Vancomycin
Loading dose, population PK, patient-specific PK, AUC monitoring
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Aminoglycosides
Gentamicin & Amikacin — MDD, SDD Hartford, neonates
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Phenytoin
Corrected concentration, Michaelis-Menten dose adjustment
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Acetaminophen
Rumack-Matthew nomogram, hepatotoxicity risk assessment
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Drug Reference
Digoxin, Lithium, Immunosuppressants, AEDs, Methotrexate
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Sampling Guide
TDM serum sampling times reference for all drugs
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About
References, disclaimer and clinical notes
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For use by qualified healthcare professionals only. All results must be interpreted in the full clinical context of the patient.
Patient Details
Results
Reference — Renal Function Classification
| Stage | CrCl (mL/min) | Dose Adjustment |
|---|---|---|
| Normal | ≥ 90 | Full dose |
| Mild impairment | 60–89 | Usually full dose |
| Moderate impairment | 30–59 | Dose reduction often needed |
| Severe impairment | 15–29 | Significant reduction needed |
| Renal failure | < 15 | Use with extreme caution |
Loading & Incremental Loading Dose
Loading Dose
Population PK — Predict Level from Dose
Uses population Ke (Matzke equation). Enter CrCl from the CrCl tab.
Estimated Levels
Patient-Specific PK — Two Measured Levels
Cpre: 30 min before dose | Cpost: 1 h after end of infusion. Collect at steady state (3rd–4th dose).
Patient PK & New Dose
Two Steady-State Concentrations (Different Doses)
Obtain two steady-state trough levels at two different doses. Used to estimate patient Vmax & Km (Michaelis-Menten).
Michaelis-Menten PK & New Dose
Two Random Levels Post 1st Dose — Renal Impaired Patients
For renally impaired patients. Obtain two random levels after the 1st dose, at least 2 half-lives apart.
Patient PK & Suggested New Dose
Therapeutic Targets & Sampling Times
| Indication | Target Trough (mcg/mL) |
|---|---|
| Non-complicated infection | 10–15 |
| Complicated infection | 15–20 |
| Continuous infusion (SS) | 15–25 |
| AUC/MIC target | 400–600 mg·h/L |
Sampling:
• Trough: 30 min before next dose (3rd–4th dose, steady state)
• Peak: 1 h after 1-h infusion completed
• After LD: 2–3 h after administration
• Continuous infusion: 12–24 h after starting (any time at SS)
• With LD: 12–24 h after LD | Without LD: 7–14 days to SS
• Trough: 30 min before next dose (3rd–4th dose, steady state)
• Peak: 1 h after 1-h infusion completed
• After LD: 2–3 h after administration
• Continuous infusion: 12–24 h after starting (any time at SS)
• With LD: 12–24 h after LD | Without LD: 7–14 days to SS
MDD — Predict Cmax & Cmin from Current Dose
Estimated Cmax & Cmin
MDD — Patient PK & New Dose
Cpre: 30 min before dose | Cpost: 30 min after 30-min infusion. Collect at steady state (3rd–4th dose).
Patient PK & Suggested New Dose
Single Daily Dose — Hartford Nomogram
SDD Dose & Interval
Neonates / Paediatrics
Neonatal Dosing
Target Ranges
| Parameter | Gentamicin | Amikacin |
|---|---|---|
| MDD Peak (Cmax) | 5–10 mcg/mL | 25–40 mcg/mL |
| MDD Trough (Cmin) | <2 mcg/mL | <10 mcg/mL |
| Synergistic Trough | <1 mcg/mL | — |
| MDD+Dialysis Trough | <2 mcg/mL | <10 mcg/mL |
| SDD Peak target | 10–30 mcg/mL | 60 mcg/mL (adjustable) |
| Neonates Peak (MDD) | 5–12 mcg/mL | 20–30 mcg/mL |
| Neonates Trough | <1 mcg/mL | <5 mcg/mL |
| Neonates+Synergy Trough | <1 mcg/mL | — |
Corrected Phenytoin Concentration
Apply correction when albumin <35 g/L or in renal failure (CrCl <25 mL/min).
Corrected Concentration
Dose Adjustment — Two Dose-Level Pairs (Michaelis-Menten)
Suggested New Dose
Therapeutic Ranges & Sampling
| Indication | Target Range |
|---|---|
| Epilepsy | 10–20 mcg/mL |
| Status epilepticus | 15–40 mcg/mL |
| Refractory status epilepticus | >70 mcg/mL |
| Psychiatric disorders | 50–125 mcg/mL |
Sampling:
• IV: 2 h after end of infusion
• Oral: At least 6 h after dose
• Dose change monitoring: 2–5 days after initiation/change
• High-risk group (enzyme-inducing drugs: CBZ, PHY, Phenobarbitone, Rifampicin; HIV; Alcoholics): more frequent monitoring
• IV: 2 h after end of infusion
• Oral: At least 6 h after dose
• Dose change monitoring: 2–5 days after initiation/change
• High-risk group (enzyme-inducing drugs: CBZ, PHY, Phenobarbitone, Rifampicin; HIV; Alcoholics): more frequent monitoring
Toxicity Assessment
For single acute ingestion only. Obtain level at 4 h post-ingestion. Unknown time: two samples 2 h apart.
Risk Assessment
Rumack-Matthew Nomogram
References: 1. MOH Malaysia, 2019. Clinical PK Pharmacy Handbook, 2nd Ed. 2. White & Rumack, 2005. AEM 45(5):563. 3. Bauer, 2008. Applied Clinical Pharmacokinetics.
Digoxin
| Indication | Target Range |
|---|---|
| Heart Failure (CHF) | 0.5–0.9 ng/mL |
| Atrial Fibrillation (AF) | 0.8–2.0 ng/mL |
| General range | 0.8–2.0 ng/mL |
Sampling: At least 6 h post dose (trough preferred; must be post-distribution phase)
Time to SS: 5–7 days (normal renal); longer in renal impairment
Toxicity >2 ng/mL — nausea, bradycardia, arrhythmia
Tube: Plain/SST (avoid EDTA — causes falsely high levels in some assays)
Time to SS: 5–7 days (normal renal); longer in renal impairment
Toxicity >2 ng/mL — nausea, bradycardia, arrhythmia
Tube: Plain/SST (avoid EDTA — causes falsely high levels in some assays)
Lithium
| Indication | Target Range |
|---|---|
| Acute mania (treatment) | 0.8–1.2 mmol/L |
| Maintenance (prophylaxis) | 0.5–1.0 mmol/L |
| General therapeutic range | 0.5–1.5 mmol/L |
Sampling: 12 h post last dose (trough) — standardized 12-h level
Time to SS: 4–5 days
Toxicity: >1.5 mmol/L — tremor, ataxia; >2.0 mmol/L — severe toxicity
Note: Narrow therapeutic index. Monitor renal function, thyroid, calcium regularly.
Time to SS: 4–5 days
Toxicity: >1.5 mmol/L — tremor, ataxia; >2.0 mmol/L — severe toxicity
Note: Narrow therapeutic index. Monitor renal function, thyroid, calcium regularly.
Immunosuppressants
⚠ EDTA tube required for Cyclosporin, Tacrolimus, and Sirolimus. Plain tube gives falsely LOW levels due to drug binding to red cells.
| Drug | Target Range | Indication |
|---|---|---|
| Cyclosporin (CSA) | ~100–500 mcg/L | Varies by organ/phase |
| Tacrolimus | 4–24 ng/mL | Varies by organ/phase |
| Sirolimus | 5–20 ng/mL | Varies by organ/phase |
Cyclosporin (CSA):
• Induction phase: ~600–1700 mcg/L (whole blood trough)
• Maintenance: ~100–500 mcg/L (indication-specific)
• Sampling: Pre-dose trough (C0), or 2 h post dose (C2 monitoring)
• Blood: Adult 3 mL, Paed 2 mL
Tacrolimus / Sirolimus:
• Sampling: Pre-dose trough (immediately before next dose)
• Ranges are indication- and centre-specific
• Time to SS: 2–4 days (Tacrolimus); 3–5 days (Sirolimus)
• ESRD affects elimination: Sirolimus t½ up to 15–20 days
• Induction phase: ~600–1700 mcg/L (whole blood trough)
• Maintenance: ~100–500 mcg/L (indication-specific)
• Sampling: Pre-dose trough (C0), or 2 h post dose (C2 monitoring)
• Blood: Adult 3 mL, Paed 2 mL
Tacrolimus / Sirolimus:
• Sampling: Pre-dose trough (immediately before next dose)
• Ranges are indication- and centre-specific
• Time to SS: 2–4 days (Tacrolimus); 3–5 days (Sirolimus)
• ESRD affects elimination: Sirolimus t½ up to 15–20 days
Antiepileptic Drugs (AEDs)
| Drug | Therapeutic Range | Sampling |
|---|---|---|
| Phenytoin | 10–20 mcg/mL | ≥6 h post oral dose |
| Phenobarbitone | 15–40 mcg/mL | Pre-dose trough |
| Carbamazepine (CBZ) | 4–12 mcg/mL | Pre-dose trough |
| Valproate (VPA) | 50–100 mcg/mL | Pre-dose trough |
| Psychiatric (VPA) | 50–125 mcg/mL | Pre-dose trough |
Time to SS:
• Phenytoin: 5–14 days (nonlinear PK — variable)
• Phenobarbitone: 2–3 weeks (induction phase)
• Carbamazepine: 2–4 days (initial); re-check after 2–4 weeks due to autoinduction
• Valproate: 2–4 days
Dose change monitoring: Recheck level 2–5 days after any dose change (except Phenobarbitone and CBZ — longer).
• Phenytoin: 5–14 days (nonlinear PK — variable)
• Phenobarbitone: 2–3 weeks (induction phase)
• Carbamazepine: 2–4 days (initial); re-check after 2–4 weeks due to autoinduction
• Valproate: 2–4 days
Dose change monitoring: Recheck level 2–5 days after any dose change (except Phenobarbitone and CBZ — longer).
Methotrexate (High-Dose)
| Time Post Infusion | Target Level (µmol/L) | Action if Above |
|---|---|---|
| 24 hours | < 10 | Continue leucovorin rescue |
| 48 hours | < 1 | Increase leucovorin if above |
| 72 hours | < 0.1 | Toxicity likely if above |
Monitoring: Obtain levels at 24, 48, 72 h post infusion start
Leucovorin rescue: Continue until MTX level <0.1 µmol/L
Hydration & urine alkalinisation (pH >7) mandatory to prevent nephrotoxicity
Renal function: Monitor SCr — impaired clearance → prolonged toxicity
Alternative cutoff: 24 h <150 µmol/L (some protocols)
Leucovorin rescue: Continue until MTX level <0.1 µmol/L
Hydration & urine alkalinisation (pH >7) mandatory to prevent nephrotoxicity
Renal function: Monitor SCr — impaired clearance → prolonged toxicity
Alternative cutoff: 24 h <150 µmol/L (some protocols)
Other Drugs — General Reference
| Drug | Target Range | Sampling Time |
|---|---|---|
| Theophylline | 10–20 mcg/mL | Trough (pre-dose) |
| Amiodarone | 0.5–2.5 mg/L | Any time (long t½) |
| Gentamicin (synergy) | 3–5 mcg/mL (peak) | 30 min post infusion |
| Flucytosine (5-FC) | 25–50 mg/L | 2 h post dose (peak) |
Blood sample notes:
• Adult: 3 mL plain tube (unless EDTA specified)
• Paediatric: 2 mL
• EDTA tube required: Cyclosporin, Tacrolimus, Sirolimus only
• Adult: 3 mL plain tube (unless EDTA specified)
• Paediatric: 2 mL
• EDTA tube required: Cyclosporin, Tacrolimus, Sirolimus only
Vancomycin
| Method | Sample | Timing |
|---|---|---|
| Intermittent — Trough | Pre-dose | 30 min before next dose (3rd–4th dose) |
| Intermittent — Peak | Post-infusion | 1 h after 1-h infusion completed |
| After Loading Dose | Post-LD | 2–3 h after administration |
| Continuous Infusion | Any time (SS) | 12–24 h after starting infusion |
| With LD | — | 12–24 h after LD |
| Without LD | — | 7–14 days (time to SS) |
Aminoglycosides — MDD
| Dose | Sample | Timing |
|---|---|---|
| 3rd or 4th dose | Trough (pre) | 30 min before dose |
| 3rd or 4th dose | Peak (post) | 30 min after 30-min infusion completed |
| 2nd dose (neonates) | 1st sample | Post 2 hours |
| 2nd dose (neonates) | 2nd sample | Post 6 hours |
Aminoglycosides — SDD (Hartford)
| Timing | Notes |
|---|---|
| 6–14 h post first dose | Random level to determine dosing interval |
| After 24 h (after 1st stat dose) or pre-HD | For renal impaired patients |
| Adults: 5–7 days | Or any two post-sampling ≥2 half-lives apart |
Not applicable if drug infused over more than 1 hour.
Phenytoin
| Route | Timing |
|---|---|
| IV | 2 h after end of infusion (if rapid concentration needed) |
| Oral | At least 6 h after dose |
| After dose change | 2–5 days after initiation/change |
Acetaminophen (Toxicity)
| Scenario | Timing |
|---|---|
| Single acute ingestion | 4 h post ingestion (minimum) |
| Unknown ingestion time | 2 samples × 2 h apart |
| Toxicity assessment | Valid for 4–24 h post-ingestion only |
Other Drugs
| Drug | Sampling Time | Time to SS |
|---|---|---|
| Digoxin | ≥6 h post dose (trough) | 5–7 days |
| Lithium | 12 h post last dose | 4–5 days |
| Cyclosporin | Pre-dose trough (C0) or 2 h post (C2) | Varies |
| Tacrolimus | Pre-dose trough | 2–4 days |
| Sirolimus | Pre-dose trough | 3–5 days |
| Phenobarbitone | Pre-dose trough | 2–3 weeks (induction) |
| Carbamazepine | Pre-dose trough | 2–4 days (re-check at 2–4 wks) |
| Valproate | Pre-dose trough | 2–4 days |
| MTX (high-dose) | 24/48/72 h post infusion | N/A |
Blood sample: Adult 3 mL · Paediatric 2 mL · Plain tube (except EDTA for Cyclosporin/Tacrolimus/Sirolimus)
References
1. Ministry of Health Malaysia, 2019. Clinical Pharmacokinetics Pharmacy Handbook, 2nd Edition.
2. White S. & Rumack B., 2005. The Acetaminophen Toxicity Equations. Annals of Emergency Medicine, 45(5):563-564.
3. Bauer L., 2008. Applied Clinical Pharmacokinetics, 2nd ed. McGraw-Hill.
4. Hartford Nomogram — Aminoglycosides Single Daily Dose.
5. Matzke GR et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother, 1984.
2. White S. & Rumack B., 2005. The Acetaminophen Toxicity Equations. Annals of Emergency Medicine, 45(5):563-564.
3. Bauer L., 2008. Applied Clinical Pharmacokinetics, 2nd ed. McGraw-Hill.
4. Hartford Nomogram — Aminoglycosides Single Daily Dose.
5. Matzke GR et al. Vancomycin pharmacokinetics in patients with various degrees of renal function. Antimicrob Agents Chemother, 1984.
Disclaimer
This application is a clinical decision support tool for use by qualified healthcare professionals only. All pharmacokinetic calculations are population-based estimates. Results must always be interpreted within the full clinical context of the individual patient. The developers accept no liability for clinical decisions made based on outputs from this tool. Always verify calculations independently with a qualified clinical pharmacist.