Clinical Pharmacokinetics

Therapeutic drug
monitoring,
calculated.

Dosing, correction and monitoring tools built for the pharmacy bench — vancomycin, aminoglycosides, phenytoin, methotrexate, acetaminophen and more.

CrCl
CrCl / IBW
Cockcroft-Gault, ideal & adjusted body weight
VAN
Vancomycin
Loading dose, population & patient-specific PK, AUC
AG
Aminoglycosides
Gentamicin & amikacin — MDD, SDD Hartford, neonates
PHT
Phenytoin
Corrected level, loading dose, Graves-Cloyd, M-M adjustment
APAP
Acetaminophen
Rumack-Matthew nomogram, hepatotoxicity risk
MTX
Methotrexate
Leucovorin rescue dose lookup, high-dose monitoring
Rx
Drug Reference
Digoxin, lithium, immunosuppressants, AEDs
TDM
Sampling Guide
Serum sampling times reference for all drugs
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About
References, disclaimer and clinical notes
For use by qualified healthcare professionals only. All results must be interpreted in the full clinical context of the patient.
CrCl / IBW
Cockcroft-Gault · Ideal & Adjusted Body Weight
Formula Reference
Ideal Body Weight (IBW) — Male
IBW = 50 + 2.3 × (height_inches − 60)
height_inches = height (cm) ÷ 2.54
Ideal Body Weight (IBW) — Female
IBW = 45.5 + 2.3 × (height_inches − 60)
Adjusted Body Weight (ABW)
ABW = IBW + 0.4 × (actual_BW − IBW)
Applied only when actual_BW > IBW × 1.2 (i.e. obese patient)
Creatinine Clearance (Cockcroft-Gault) ⚠ verify
CrCl = (140 − age) × weight ÷ (0.814 × SCr)
age = patient age in years
weight = ABW if obese, otherwise actual body weight (kg)
SCr = serum creatinine in µmol/L
Result × 0.85 if patient is female
Source: Cockcroft-Gault equation, 1976. Coefficient 0.814 = 72 ÷ 88.4 (mg/dL→µmol/L conversion).
Patient Details
Results
Reference — Renal Function Classification
StageCrCl (mL/min)Dose Adjustment
Normal≥ 90Full dose
Mild impairment60–89Usually full dose
Moderate impairment30–59Dose reduction often needed
Severe impairment15–29Significant reduction needed
Renal failure< 15Use with extreme caution
Vancomycin
Loading Dose · Population PK · Patient-specific PK
Formula Reference — Vancomycin
Loading Dose
LD = dose_per_kg × weight  (15–20 or 25–30 mg/kg)
weight = actual body weight (kg)
Incremental Loading Dose
Incremental LD = (C_desired − C_current) × 0.7 × weight
C_desired / C_current = target / measured level (mcg/mL) · 0.7 = population Vd (L/kg)
Elimination Rate Constant (Ke) — Population (Matzke) ⚠ verify
Ke = 0.00083 × CrCl + 0.0044
CrCl = creatinine clearance (mL/min)
Source: Matzke GR et al., Antimicrob Agents Chemother, 1984.
Half-life / Volume of Distribution
t½ = 0.693 ÷ Ke   |   Vd = 0.7 × weight (L)
Cmax / Cmin (Steady-State)
Cmax = (D÷t_inf)×(1−e^(−Ke×t_inf)) ÷ (Ke×Vd×(1−e^(−Ke×τ)))
Cmin = Cmax × e^(−Ke×(τ−t_inf))
D = dose (mg) · t_inf = infusion time (h) · τ = dosing interval (h)
AUC₂₄
AUC₂₄ = (D ÷ Vd ÷ Ke) × (24 ÷ τ)
Target range: 400–600 mg·h/L
Patient-Specific Ke (2-level method)
Ke = ln(Cpost ÷ Cpre) ÷ (t_post − t_pre)
Cpre / Cpost = trough / peak level (mcg/mL) · t_pre / t_post = sample times (h)
New Dose (from patient PK)
D_new = C_target×Ke×Vd×(1−e^(−Ke×τ)) ÷ ((1−e^(−Ke×t_inf))×e^(−Ke×(τ−t_inf)))
C_target = desired trough level (mcg/mL)
Two Steady-State / Two Random Levels (Michaelis-Menten)
Km = (D1×L2 − D2×L1) ÷ (D2 − D1)  |  Vmax = D1×(Km+L1)÷L1
D_new = Vmax × C_desired ÷ (Km + C_desired)
D1, D2 = two different doses · L1, L2 = corresponding steady-state levels
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
One Steady-State Concentration
Obtain one steady-state trough level. Use population Vd (0.7 L/kg) to back-calculate patient Ke, then suggest new dose.
Estimated 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
IndicationTarget Trough (mcg/mL)
Non-complicated infection10–15
Complicated infection15–20
Continuous infusion (SS)15–25
AUC/MIC target400–600 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: 7–10 days (normal renal) / 7–14 days (renal impaired)
Aminoglycosides
Gentamicin · Amikacin · MDD · SDD · Neonates
Formula Reference — Aminoglycosides
Elimination Rate Constant (Ke) — Population ⚠ verify
Ke = 0.00293 × CrCl + 0.014
CrCl = creatinine clearance (mL/min)
Volume of Distribution (Vd)
Vd (Gentamicin) = 0.26 × weight  |  Vd (Amikacin) = 0.25 × weight
weight = body weight (kg)
Cmax / Cmin (Steady-State, MDD)
Cmax = (D÷t_inf)×(1−e^(−Ke×t_inf)) ÷ (Ke×Vd×(1−e^(−Ke×τ)))
Cmin = Cmax × e^(−Ke×(τ−t_inf))
D = dose (mg) · t_inf = infusion time (h) · τ = dosing interval (h)
Patient-Specific Ke & New Dose (MDD)
dt = τ − t_inf − 0.5  |  Ke = ln(Cpost ÷ Cpre) ÷ dt
D_new = D_current × (C_target ÷ Cpost)
Cpre / Cpost = measured trough / peak (mcg/mL) · 0.5 h = sampling delay after infusion
Suggested Dosing Interval
τ_new = round(3 × t½ ÷ 6) × 6
Rounds interval to nearest practical 6-hour block (≈3 half-lives)
SDD Hartford — Dose
Dose (Gentamicin) = 5 mg/kg × ABW  |  Dose (Amikacin) = 15 mg/kg × ABW
SDD Hartford — Interval (by CrCl)
CrCl ≥60 → q24h  |  40–59 → q36h  |  <40 → q48h
Confirmed using random level taken 6–14 h post-dose against Hartford nomogram
Neonatal Dosing
Fixed dose/interval bands by gestational age (GA) and postnatal age (PNA) — see table in Neonates tab. Not formula-derived; based on published paediatric dosing protocols.
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
ParameterGentamicinAmikacin
MDD Peak (Cmax)5–10 mcg/mL25–40 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 target10–30 mcg/mL60 mcg/mL (adjustable)
Neonates Peak (MDD)5–12 mcg/mL20–30 mcg/mL
Neonates Trough<1 mcg/mL<5 mcg/mL
Neonates+Synergy Trough<1 mcg/mL
MDD + Dialysis Trough<2 mcg/mL<10 mcg/mL
DFP (Dosing Frequency Period):
• Gentamicin DFP: interval based on CrCl — used in SDD Hartford nomogram
• Amikacin DFP: similarly interval-based
• Target DFP is read from Hartford nomogram (6–14 h post-dose level)
Phenytoin
Corrected Concentration · Dose Adjustment
Formula Reference — Phenytoin
Step 1 — Check Albumin (assume normal if unavailable)
Albumin ≥ 2.5 g/dL → no correction needed, use measured level directly
Step 2 — If Albumin < 2.5 g/dL: Corrected Concentration (CrCl ≥10 mL/min or unknown)
C_corrected = C_measured ÷ (0.9 × (Albumin ÷ 4.4) + 0.1)
C_measured = lab-reported total phenytoin level (mcg/mL)
Albumin = serum albumin (g/dL)
Step 2 — If Albumin < 2.5 g/dL AND CrCl < 10 mL/min
C_corrected = C_measured ÷ (0.48 × 0.9 × (Albumin ÷ 4.4) + 0.1)
Dose Adjustment (Michaelis-Menten, two dose-level pairs)
Km = (D1×L2 − D2×L1) ÷ (D2 − D1)
Vmax = D1 × (Km + L1) ÷ L1
D_new = Vmax × C_desired ÷ (Km + C_desired)
D1, D2 = two doses tried (mg/day) · L1, L2 = corresponding corrected steady-state levels (mcg/mL) · C_desired = target level
Loading Dose — Phenytoin-naïve / Incremental (already on phenytoin)
Naïve: LD = Cp_desired × Vd × BW ÷ (S × F)
Incremental: LD = (Cp_desired − Cp_measured) × Vd × BW ÷ (S × F)
Vd = volume of distribution (L/kg) — enter manually (guide ranges: Neonate premature 1–1.2, term 0.8–0.9 · Infant 0.7–0.8 · Pediatric 0.7 · Adult 0.65–0.7 L/kg)
S = salt factor (IV/Capsule 0.92, Susp/Chew Tab 1) · F = bioavailability (all routes = 1)
Graves-Cloyd Method — Single-Level Dose Adjustment
D_new = D_old × (Css_desired ÷ Css_old)0.2
D_old = current dose (mg/day) · Css_old = current steady-state level (mcg/mL) · Css_desired = target level (mcg/mL)
Verified against Graves NM et al., Ther Drug Monit 1986;8(4):427-33 (original exponent 0.2, n=59). A later re-analysis of the same dataset reported b=−0.804, i.e. exponent 0.196 — essentially the same value. The "0.199" in the source slide appears to be an OCR/legibility artifact of 0.2/0.196.
Time to Withhold Therapy — Toxic Level → Desired Level
T (days) = [Km × ln(Cp_measured ÷ Cp_desired) + (Cp_measured − Cp_desired)] × Vd ÷ Vm
Cp_measured = current toxic level · Cp_desired = target level (mcg/mL) · Vd = Vd/kg × body weight (L) · Vm = Vm/kg × body weight (mg/day) · Km in mg/L
Adult — Local population: Vm 8.45 mg/kg/day, Km 6.72 mg/L  |  Adult — Literature: Vm 7 mg/kg/day, Km 4 mg/L
Infant: Vm 10–14 mg/kg/day (midpoint 12 used), Km 6 mg/L
Vd: Adult 0.65–0.7 L/kg (midpoint 0.675) · Infant 0.7–0.8 L/kg (midpoint 0.75)
⚠ Pediatric/Neonatal Km & Vm not provided in source guide — calculator currently supports Adult and Infant only.
Corrected Phenytoin Concentration
Always check Albumin (and CrCl/BUSE-Creat) first — if unavailable, assume normal. If Albumin ≥2.5 g/dL: no correction needed, use the measured level as-is. If Albumin <2.5 g/dL, the correction equation is applied automatically below (renal-failure variant only if CrCl is also <10 mL/min).
Corrected Concentration
Loading Dose — Naïve / Incremental
Leave Cp Measured blank for a phenytoin-naïve patient (uses the naïve formula). Enter a value to calculate an incremental loading dose for a patient already on phenytoin. Vd is entered manually — guide ranges: Neonate premature 1–1.2, term 0.8–0.9 · Infant 0.7–0.8 · Pediatric 0.7 · Adult 0.65–0.7 L/kg.
Loading Dose
Dose Adjustment — Two Dose-Level Pairs (Michaelis-Menten)
Suggested New Dose
Graves-Cloyd Method — Single-Level Dose Adjustment
Uses a single steady-state level (instead of two dose-level pairs) to predict a new dose. Formula verified against Graves NM et al., Ther Drug Monit 1986;8(4):427-33 (exponent 0.2).
Suggested New Dose
Time to Withhold Therapy — Toxic Phenytoin Level
For use when the level is in the toxic range and therapy needs to be withheld until it decays to a safe/desired level (Michaelis-Menten elimination). Km/Vm data is only available for Adult and Infant in the source guide — Pediatric/Neonatal values were not provided, so this calculator does not cover those groups yet.
Time to Withhold Therapy
Therapeutic Ranges & Sampling
IndicationTarget Range
Epilepsy10–20 mcg/mL
Status epilepticus15–40 mcg/mL
Refractory status epilepticus>70 mcg/mL
Psychiatric disorders50–125 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
Acetaminophen
Rumack-Matthew Nomogram
Formula Reference — Acetaminophen
Rumack-Matthew Treatment Line
Treatment_line = 150 × 10^(−(t−4) × log₁₀(150÷4.7) ÷ 20)
t = hours post-ingestion (valid range: 4–24 h only)
Line passes through 150 mcg/mL at 4 h and 4.7 mcg/mL at 24 h
Possible Risk Line
Risk_line (standard) = Treatment_line × 0.75
Risk_line (high-risk group) = Treatment_line × 0.50
High-risk = enzyme inducers, chronic alcohol use, malnutrition/fasting
Source: White S. & Rumack B., Annals of Emergency Medicine, 2005.
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.
Methotrexate
Leucovorin Rescue · High-Dose MTX Monitoring
Sampling time is based on the patient's specific MTX protocol — typically 24, 48, 72 (and 96) hours post-infusion start.
Leucovorin Rescue Dose Lookup
Leucovorin Recommendation
Leucovorin Rescue Protocol Summary
HoursMTX (µmol/L)Leucovorin (mg/m² QID)
Post 24 h10.1–1290
Post 24 h12.1–18150
Post 24 h>18300
Post 48 h1.1–1.815
Post 48 h1.9–2.830
Post 48 h2.9–8.590
Post 48 h8.6–18150
Post 48 h>18300
Post 72 h0.1–0.2910
Post 72 h0.3–1.815
Post 72 h1.9–2.830
Post 72 h2.9–9.890
Post 72 h9.9–19150
Post 72 h>19300
Post 96 hSame brackets as 72 h
At 96 h, refer to the same concentration brackets as 72 h. Further serum MTX levels may be done daily thereafter.
Acceptable Range — High-Dose Methotrexate
TimeAcceptable Level
24 hours5–10 µmol/L
48 hours0.5–1 µmol/L
72 hours<0.1 µmol/L
Random<0.05 µmol/L (undetectable)
Sampling: Based on the patient's specific protocol.
Hydration & urine alkalinisation (pH >7) mandatory throughout to prevent nephrotoxicity.
Renal function: Monitor SCr — impaired clearance prolongs MTX exposure and toxicity risk.
Drug Reference
Therapeutic ranges · Sampling times
Digoxin
IndicationTarget Range
Heart Failure (CHF)0.5–0.9 ng/mL
Atrial Fibrillation (AF)0.8–2.0 ng/mL
General range0.8–2.0 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)
Lithium
IndicationTarget Range
Acute mania (treatment)0.8–1.2 mmol/L
Maintenance (prophylaxis)0.5–1.0 mmol/L
General therapeutic range0.5–1.5 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.
Immunosuppressants
⚠ EDTA tube required for Cyclosporin, Tacrolimus, and Sirolimus. Plain tube gives falsely LOW levels due to drug binding to red cells.
DrugTarget RangeIndication
Cyclosporin (CSA)~100–500 mcg/LVaries by organ/phase
Tacrolimus4–24 ng/mLVaries by organ/phase
Sirolimus5–20 ng/mLVaries 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
Antiepileptic Drugs (AEDs)
DrugTherapeutic RangeSampling
Phenytoin10–20 mcg/mL≥6 h post oral dose
Phenobarbitone15–40 mcg/mLPre-dose trough
Carbamazepine (CBZ)4–12 mcg/mLPre-dose trough
Valproate (VPA)50–100 mcg/mLPre-dose trough
Psychiatric (VPA)50–125 mcg/mLPre-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).
Methotrexate (High-Dose)
For the full Leucovorin rescue dose lookup calculator, see the dedicated Methotrexate module on the home screen.
Time Post InfusionAcceptable Level (µmol/L)
24 hours5–10
48 hours0.5–1
72 hours< 0.1
Random< 0.05 (undetectable)
Sampling: Based on patient's specific protocol; levels typically at 24, 48, 72 (and 96) 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
Other Drugs — General Reference
DrugTarget RangeSampling Time
Theophylline10–20 mcg/mLTrough (pre-dose)
Amiodarone0.5–2.5 mg/LAny time (long t½)
Gentamicin (synergy)3–5 mcg/mL (peak)30 min post infusion
Flucytosine (5-FC)25–50 mg/L2 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
Sampling Guide
TDM Serum Sampling Times
Vancomycin
MethodSampleTiming
Intermittent — TroughPre-dose30 min before next dose (3rd–4th dose)
Intermittent — PeakPost-infusion1 h after 1-h infusion completed
After Loading DosePost-LD2–3 h after administration
Continuous InfusionAny time (SS)12–24 h after starting infusion
With LD12–24 h after LD
Without LD7–14 days (time to SS)
Aminoglycosides — MDD
DoseSampleTiming
3rd or 4th doseTrough (pre)30 min before dose
3rd or 4th dosePeak (post)30 min after 30-min infusion completed
2nd dose (neonates)1st samplePost 2 hours
2nd dose (neonates)2nd samplePost 6 hours
Aminoglycosides — SDD (Hartford)
TimingNotes
6–14 h post first doseRandom level to determine dosing interval
After 24 h (after 1st stat dose) or pre-HDFor renal impaired patients
Adults: 5–7 daysOr any two post-sampling ≥2 half-lives apart
Not applicable if drug infused over more than 1 hour.
Phenytoin
RouteTiming
IV2 h after end of infusion (if rapid concentration needed)
OralAt least 6 h after dose
After dose change2–5 days after initiation/change
Acetaminophen (Toxicity)
ScenarioTiming
Single acute ingestion4 h post ingestion (minimum)
Unknown ingestion time2 samples × 2 h apart
Toxicity assessmentValid for 4–24 h post-ingestion only
Other Drugs
DrugSampling TimeTime to SS
Digoxin≥6 h post dose (trough)5–7 days
Lithium12 h post last dose4–5 days
CyclosporinPre-dose trough (C0) or 2 h post (C2)Varies
TacrolimusPre-dose trough2–4 days
SirolimusPre-dose trough3–5 days
PhenobarbitonePre-dose trough2–3 weeks (induction)
CarbamazepinePre-dose trough2–4 days (re-check at 2–4 wks)
ValproatePre-dose trough2–4 days
MTX (high-dose)24/48/72 h post infusionN/A
Blood sample: Adult 3 mL · Paediatric 2 mL · Plain tube (except EDTA for Cyclosporin/Tacrolimus/Sirolimus)
About
References & Disclaimer
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.

6. Rozario F.D., Soo H.H., Hu M., Chew P.H., 2020. Sarawak Handbook of Medical Emergencies, 4th Ed. Malaysia: CE Publishing.
Credits
© All rights reserved.
Created by Charlie Ting  ·  Validated by Pharmacist Rachel Wang Li Ting
⚠ For clinical use by trained pharmacists only. Always verify calculations independently.
This application is a clinical decision support tool. 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.
© All rights reserved.
Created by Charlie Ting  ·  Validated by Pharmacist Rachel Wang Li Ting
⚠ For clinical use by trained pharmacists only. Always verify calculations independently.