BACKGROUND: Tacrolimus is a potent calcineurin inhibitor (CNI) that is principally used as a first-line immunosuppressant for the prophylaxis of allograft rejection in liver transplantation (LT) patients. In clinical practice, prescribing the optimal tacrolimus dosage is complicated by its narrow therapeutic index and high pharmacokinetic variability. Thus, performing therapeutic drug monitoring (TDM) of only tacrolimus may not provide optimal drug levels. However, other influential clinical factors affecting tacrolimus levels, such as hemoglobin (Hb), hematocrit, and total bilirubin (TBIL), should be considered while adjusting tacrolimus levels. This case report aims to introduce clinicians and their teams to taking the pharmacokinetic prediction equation into consideration for a better understanding of tacrolimus dosage adjustment during the early postoperative LT.
METHODS: In this case report, an 18-year-old male patient of Thai ethnicity was admitted for orthotropic liver transplantation, and tacrolimus was prescribed as a cornerstone immunosuppressive agent. In the immediate postoperative period, which is the most challenging period in liver transplantation, the population pharmacokinetics predictive equation was clinically used to assist in dosage adjustment of tacrolimus by considering the significant clinical factors in this case. Hemoglobin and total bilirubin levels were deemed significant clinical factors affecting the oral clearance (CL/F) of tacrolimus. First, a decrease in the Hb concentration increases the free drug concentration and therefore increases the CL/F of tacrolimus. Second, an elevated TBIL decreases the biliary excretion of tacrolimus, resulting in a decrease in the CL/F of tacrolimus. Thus, dose optimization of tacrolimus would be accurate when taking the pharmacokinetic prediction equation into consideration. Moreover, the results may contribute to a better understanding of tacrolimus pharmacokinetic variability in each transplant patient during the immediate postoperative course.
CONCLUSIONS: Hemoglobin and total bilirubin were significant clinical factors influencing the oral clearance of tacrolimus early after liver transplantation. A decrease in the hemoglobin concentration would increase the free drug concentration and therefore increase the oral clearance of tacrolimus. An elevated total bilirubin decreases the biliary excretion of tacrolimus, resulting in a decrease in the oral clearance of tacrolimus.

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OBJECTIVE: Preliminary evidence shows that concomitant administration of valproic acid can reduce the exposure to dolutegravir with limited clinical impacts. Here, we describe a male living with HIV who experienced a drastic reduction in dolutegravir trough concentrations a few weeks after starting valproic acid treatment as identified by therapeutic drug monitoring. Concomitantly, pharmacists recommended a supplementation of magnesium to improve insomnia.
METHODS: A 62-year-old man with HIV on antiretroviral therapy with dolutegravir and lamivudine recently added valproic acid to clonazepam and sertraline to treat severe sleep disturbances. An 84% reduction in dolutegravir trough concentrations was observed compared with the previous outpatient visit (418 versus 2714 ng/mL), with values close to the minimum effective drug concentration (300 ng/mL). Considering this, we strongly discourage the use of magnesium.
CONCLUSIONS: We are confident that our findings can contribute to a better understanding of the clinical problems that infectious disease physicians encounter in their daily management of people with HIV and how therapeutic drug monitoring may add value in this context. This case also highlights the importance of multidisciplinary services for the optimal management of polypharmacy in people with HIV.

Implant-related infections may need suppressive antibiotic therapy (SAT). We describe a SAT strategy using dalbavancin with therapeutic drug monitoring (TDM). This is a retrospective bicentric study of patients with implant-related infection who received dalbavancin SAT between January 2021 and September 2023. Fifteen patients were included. Median number of injections was 4 (IQR: 2-7). Median time between two reinjections was 57 days (IQR 28-82). Dalbavancin plasma concentrations were above 4 mg/L for 97.9% of dosages (93/95) and above 8 mg/L for 85% (81/95). These results support the use of dalbavancin SAT for implant-related infections.

UNASSIGNED: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations.
METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia.
RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses.
CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

BACKGROUND: Pregnant patients with epilepsy are prone to preterm delivery, stillbirth, or cesarean section, and their mortality rate is almost 10 times higher than that of normal pregnant women. The potential negative influences of antiepileptic drugs (AEDs) on the fetus are weighed against the necessity for achieving optimal control of seizures. Treatment with AEDs during pregnancy is a major challenge for pregnant women and healthcare teams.
METHODS: This paper reports two cases of young women diagnosed with pregnancy and epilepsy.
METHODS: The dose of levetiracetam was adjusted under the guidance of therapeutic drug monitoring to reduce the effects of seizures on the fetus and the incidence of reproductive toxicity caused by adverse drug reactions.
RESULTS: Epilepsy was well controlled in the two pregnant patients, and the newborns had no genetic disorders.
CONCLUSIONS: It is recommended to regularly monitor the serum LEV level in pregnant patients with epilepsy. This practice serves as a foundation for adjusting the drug treatment plan and offering more precise guidance for medication management during pregnancy.

Warfarin dosing remains challenging due to substantial inter-individual variability, which can lead to unsafe or ineffective therapy with standard dosing. Model-informed precision dosing (MIPD) can help individualize warfarin dosing, requiring the selection of a suitable model. For models developed from clinical data, the dependence on the study design and population raises questions about generalizability. Quantitative system pharmacology (QSP) models promise better extrapolation abilities; however, their complexity and lack of validation on clinical data raise questions about applicability in MIPD. We have previously derived a mechanistic warfarin/international normalized ratio (INR) model from a blood coagulation QSP model. In this article, we evaluated the predictive performance of the warfarin/INR model in the context of MIPD using an external dataset with INR data from patients starting warfarin treatment. We assessed the accuracy and precision of model predictions, benchmarked against an empirically based reference model. Additionally, we evaluated covariate contributions and assessed the predictive performance separately in the more challenging outpatient data. The warfarin/INR model performed comparably to the reference model across various measures despite not being calibrated with warfarin initiation data. Including CYP2C9 and/or VKORC1 genotypes as covariates improved the prediction quality of the warfarin/INR model, even after assimilating 4 days of INR data. The outpatient INR exhibited higher unexplained variability, and predictions slightly exceeded observed values, suggesting that model adjustments might be necessary when transitioning from an inpatient to an outpatient setting. Overall, this research underscores the potential of QSP-derived models for MIPD, offering a complementary approach to empirical model development.

UNASSIGNED: The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was necessary to achieve adequate drug exposure and improve kidney function.

BACKGROUND: An increasing use of newer antiseizure medication (ASM) such as SV2A ligand brivaracetam is observed. However, data on newer antiseizure medication and therapeutic drug monitoring during pregnancy is scarce.
METHODS: Therapeutic drug monitoring of brivaracetam (BRV) and topiramate (TPM) serum levels were performed during pregnancy, delivery and in the umbilical cord blood at delivery in a 34-year-old female patient with severe drug-resistant epilepsy.
RESULTS: During pregnancy, the serum levels of brivaracetam and topiramate remained stable. At 39th week of pregnancy, the patient gave birth to a healthy daughter. 1.5 h after the last ASM intake, the penetration rate measured in umbilical cord blood was 45% lower for BRV and 35% lower for TPM.
CONCLUSIONS: While the pharmacokinetics of topiramate are well known and its use during pregnancy should only be undertaken under special circumstances, there have been few studies on newer ASM in pregnancy such as brivaracetam. Based on our results and other case reports of BRV use during pregnancy, further studies are necessary to confirm its pharmacokinetics and safety during pregnancy.