Therapeutic drug monitoring · 2026
Intertwin Amikacin Exposure in Conjoined Twins: A Therapeutic Drug Monitoring-Informed Coupled Pharmacokinetic Modeling Case Study.
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Tezel-Yalçın Hülya, İyigün İrem, Çelik Hasan Tolga, Allegaert Karel, Yalçın Nadir
Аннотация
BACKGROUND: Conjoined twins represent a rare condition in which drug exposure may be influenced by shared circulation and organ anatomy. For narrow therapeutic index antimicrobials such as amikacin, therapeutic drug monitoring (TDM) may require interpretation at twin-pair level.
METHODS: A retrospective TDM-informed coupled compartmental pharmacokinetic modeling study of 2 conjoined twin pairs was performed. One pair was pygopagus, and both twins (A and B) received amikacin treatment. The other pair was thoracopagus (X and Y) with complex shared cardiothoracic anatomy; amikacin was administered to twin X but not to twin Y. Data were reviewed and structured for pharmacokinetic modeling. Amikacin disposition was evaluated using a model incorporating twin-specific disposition and intertwin transfer.
RESULTS: The pygopagus twins both received amikacin (35 mg) intravenously every 24 hours, corresponding to approximately 14.2 mg/kg/d. Paired concentrations showed asymmetric exposure despite identical nominal dosing: peak concentrations were 7.7 and 13.1 mg/L, and trough concentrations were 4.0 and 2.7 mg/L in twins A and B, respectively. Twin X received amikacin (85 mg; 15 mg/kg/d) intravenously every 24 hours during the first dosing period, followed by a single dose (83 mg) 3 days later. Approximately 69 hours after the last dose, the concentrations were 5.3/L and 10.9 mg/L in twin X and twin Y, respectively. A no-transfer model predicted no amikacin exposure in twin Y. Representative coupled solutions supported intertwin transfer in the 10-2 L/h range, and compatible Qtransfer values of approximately 0.016-0.066 L/h were identified, indicating that no single transfer clearance value was uniquely identifiable from the 2 case 2 concentrations.
CONCLUSIONS: This analysis illustrates how paired TDM and a literature-anchored coupled compartmental pharmacokinetic model can support drug exposure interpretation in exceptional clinical settings where conventional modeling is not feasible.
METHODS: A retrospective TDM-informed coupled compartmental pharmacokinetic modeling study of 2 conjoined twin pairs was performed. One pair was pygopagus, and both twins (A and B) received amikacin treatment. The other pair was thoracopagus (X and Y) with complex shared cardiothoracic anatomy; amikacin was administered to twin X but not to twin Y. Data were reviewed and structured for pharmacokinetic modeling. Amikacin disposition was evaluated using a model incorporating twin-specific disposition and intertwin transfer.
RESULTS: The pygopagus twins both received amikacin (35 mg) intravenously every 24 hours, corresponding to approximately 14.2 mg/kg/d. Paired concentrations showed asymmetric exposure despite identical nominal dosing: peak concentrations were 7.7 and 13.1 mg/L, and trough concentrations were 4.0 and 2.7 mg/L in twins A and B, respectively. Twin X received amikacin (85 mg; 15 mg/kg/d) intravenously every 24 hours during the first dosing period, followed by a single dose (83 mg) 3 days later. Approximately 69 hours after the last dose, the concentrations were 5.3/L and 10.9 mg/L in twin X and twin Y, respectively. A no-transfer model predicted no amikacin exposure in twin Y. Representative coupled solutions supported intertwin transfer in the 10-2 L/h range, and compatible Qtransfer values of approximately 0.016-0.066 L/h were identified, indicating that no single transfer clearance value was uniquely identifiable from the 2 case 2 concentrations.
CONCLUSIONS: This analysis illustrates how paired TDM and a literature-anchored coupled compartmental pharmacokinetic model can support drug exposure interpretation in exceptional clinical settings where conventional modeling is not feasible.