Research digest: The benefits of therapeutic drug monitoring in hypertension

25th September 2024

Therapeutic drug monitoring (TDM) can be useful in monitoring non-adherence in patients with hypertension to improve blood pressure control. It can also optimise antihypertensive drug (AHD) treatment in specific patient groups, such as female versus male or elderly patients, where their pharmacokinetic parameters are altered.

In a new review article, clinicians at the University Medical Centre Rotterdam examined the challenges around non-adherence and highlighted how TDM can be used to manage hypertension. 

AHDs do not usually qualify as optimal candidates for TDM because of their physiological effect, poor correlation between blood concentrations and therapeutic outcomes, and wide therapeutic range. Despite the availability of several categories of AHDs with different drug makeups, a significant proportion of patients with hypertension remains poorly controlled with a ‘one-size fits all’ approach often used, the researchers said.

Optimising therapy with TDM

The review cites research showing that TDM alone will not improve adherence and highlights the need for additional interventions, such as personalised feedback sessions with patients to discuss the results of the AHD concentrations measured by TDM.

TDM of AHDs can also offer benefits in optimising therapy for specific populations. Females exhibit higher peak concentrations of metoprolol and have a higher average exposure time to the drug (area under the curve, AUC) compared to males. However, there have been a limited number of studies that use TDM to investigate the underlying differences in how each sex responds to AHDs, but the work so far shows that TDM for AHDs might be useful.

Another population where TDM is used to optimise AHD treatment is the elderly. Recent work indicates that elderly patients would benefit from lower AHD dosages than are currently available on the market. In addition, further work shows that a population pharmacokinetic model could be used to predict the correct starting dose in elderly patients with hypertension.

Potential for individualised treatment

TDM is perceived as a costly method, however, concentrating measurements in specialist hospitals would cut costs and increase efficiency and expertise, the researchers said.

Having reviewed recent developments, the researchers stated that ‘the journey of AHD TDM is just beginning’. TDM could provide valuable insights into the optimal AHD and dose and offer the potential to individualise treatment, benefitting specific patient groups and helping others adhere to AHD therapy.

Reference
Versmissen, J et al. ‘Under pressure’: The role of therapeutic drug monitoring in the treatment of hypertension. British Journal of Clinical Pharmacology. 2024; 90(8): 1884-1891. doi: 10.1111/bcp.16125doi.org/10.1111/bcp.16125.

Exhaled breath analysis shows promise for monitoring antibiotic concentrations

3rd May 2024

Exhaled breath analysis shows promise as a non-invasive approach for the therapeutic monitoring of antibiotics, a proof-of-concept study has found.

At the recent ESCMID Global Congress Barcelona, Spain (27-30 April), Swiss researchers presented the findings from the prospective, single-centre study of 10 adult hospitalised patients (median age 63 years, 54.5% female) who received intravenous antibiotic treatment in 2022 or 2023.

For patients with severe infections or in intensive care, therapeutic drug monitoring allowed clinicians to account for differences in how individuals metabolise drugs and was used to optimise and guide dosing.

First author Dr Sarah Dräger, senior physician in the Division of Internal Medicine at University Hospital Basel in Switzerland, said drugs were usually monitored through testing blood samples but the process was invasive, time-consuming and lead to patient discomfort.

‘It takes several hours or even days to get results, depending on the antibiotic tested, and so the results may come too late to guide the treatment of some of the sickest patients,’ she said.

In contrast, breath samples were easy to collect, Dr Dräger said, adding the method was non-invasive and not associated with patient discomfort.

The approach could also decrease turnaround times, with results potentially being available in 10 minutes.

‘[Exhaled breath analysis] is already used to monitor other drugs, such as antiseizure medicines, and we wanted to explore its potential in monitoring antibiotics,’ Dr Dräger said.

Patients in the study were being treated for respiratory infections (n=3), intravascular infections (n=3), abdominal infections (n=2), urinary tract infection (n=1) or skin and soft tissue infection (n=1).

The antibiotics used were meropenem (n=3), piperacillin/tazobactam (n=3), cefazolin (n=2), flucloxacillin (n=1) and ciprofloxacin (n=1), the researchers reported in a poster at the conference.

Plasma therapeutic drug monitoring samples were collected 0-60 minutes after the end of the antibiotic bolus infusion.

Some 30 minutes after the blood sample collection, researchers performed exhaled breath analysis using secondary electrospray ionisation (SESI) combined with high resolution mass spectrometry (HRMS).

SESI-HRMS, a real-time exhaled breath analysis technique, was characterised by a high sensitivity and broad metabolic coverage, including endogenous (breakdown products from the antibiotic) and exogenous (breakdown products from the body that are affected by the antibiotic) metabolites.

The breath analysis identified specific exhaled molecules associated with meropenem, cefazolin, flucloxacillin and ciprofloxacin, but there was no clear signal for piperacillin.

Dr Dräger concluded: ‘We were able to detect antibiotic-specific metabolites in exhaled breath in patients treated with antibiotics in four out of five antibiotics investigated.

‘We aim to confirm these very promising results in a larger cohort of patients, as well as look at how they relate to blood plasma concentrations of antibiotics and patient outcomes.’

Monitoring adalimumab levels valuable for assessing remission in children with Crohn’s disease

9th June 2021

Adalimumab is effective for children with Crohn’s disease but little is known about the impact of therapeutic monitoring on clinical outcomes.

The clinical symptoms of Crohn’s disease (CD) are similar in adults and children although there is evidence that cases of paediatric CD are on the rise, with one study estimating that the highest incidence, at 23 per 100,000 person-years occurred in Europe.

Endoscopic evidence of mucosal healing is a valuable therapeutic goal that decreases the risk of disease relapse although little is known about the association between mucosal healing and therapeutic levels of biological treatments such as adalimumab.

This prompted a team from the Department of Paediatrics, Samsung Medical Centre, Korea, to examine the relationship between therapeutic drug monitoring of adalimumab and mucosal healing and clinical remission in paediatric patients with CD.

The team prospectively recruited paediatric patients with CD receiving adalimumab maintenance therapy and who underwent routine endoscopic evaluation of mucosal healing and therapeutic drug monitoring. Monitoring assessments were made at four months and then at years one, two and three.

Findings

In total, 31 children with a mean age of 14.8 years (74% male) were included in the analysis. After one year of treatment, 26 (83.9%) had achieved clinical remission and 17 (54.8%) had complete mucosal healing.

The mean adalimumab trough levels were higher in patients who had achieved remission compared to those with active disease (7.6 mcg/ml vs 5.1 mcg/ml, remission vs active disease).

Similarly, trough levels of adalimumab were significantly higher in those who achieved mucosal healing after one year (14.2 mcg/ml vs 7.8mcg/ml, mucosal healing vs non-healed, p = 0.03).

Although only 23 children were evaluated after 3 years, adalimumab trough levels remained above 10 mcg/ml and a similar proportion of children maintained mucosal healing (64.3%) and clinical remission (92.9%).

Using receiver operating curves, authors calculated that the optimal cut-off adalimumab trough levels to achieve mucosal healing was 8.18 mcg/ml.

In discussing their findings, the authors commented on the results demonstrated that mucosal healing rates increased when adalimumab was used over the longer term and that the drug maintained its efficacy.

They concluded that there was merit in using therapeutic drug monitoring to guide proactive optimisation of drug levels to achieve the goal of mucosal healing.

Citation
Kim MJ et al. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients with Crohn Disease. JPGN 2021;72:870-6.