Available online on 15.03.2026 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2026 The   Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access Full Text Article   Research Article

Pharmacological Therapeutic Monitoring of Three Major Anti-Epileptic Drugs in Mali

Mohamed TOURE ^1,2, Adama Seydou SISSOKO ^2,3, Mahamadou BALLO ¹, Sékou BAH ^1,2

¹ Faculty of Pharmacy, USTTB, Mali

² Point G University Hospital Centre

³ Faculty of Medicine and Odontostomatology, USTTB, Mali

 

 

INTRODUCTION

Epilepsy is a chronic neurological condition characterised by recurrent epileptic seizures in the same individual. These seizures may be related to an imbalance between excitatory and inhibitory neurotransmitters, causing excessive and hyper-synchronous neuronal discharges within the cerebral cortex ¹. The probability of an individual developing epilepsy during their lifetime varies between 3% and 5%. Newborns, children and the elderly are at greater risk of developing epilepsy ^1,2,2. Epilepsy affects approximately 50 million people worldwide, or 1 to 3% of the global population. In the US, the prevalence of epilepsy is estimated at between 330 and 380 per 100,000 inhabitants; in France, it is between 380 and 430 per 100,000 inhabitants; and in Mali, it is between 230 and 280 per 100,000 inhabitants. Sub-Saharan Africa accounts for 80% of the global epileptic population, with a prevalence of 15.4% ^1,3. 

Antiepileptic drugs are used to reduce the frequency and/or severity of seizures in patients with epilepsy. Most of them have shown significant pharmacokinetic variability. Most of them showed significant pharmacokinetic variability. For this reason, therapeutic drug monitoring, which involves measuring and interpreting drug concentrations in the blood in order to determine the correct dose of medication for a given patient, is recommended ⁴. This individualized approach takes into account the specific characteristics of patients or their disease and optimizes treatment by maximizing efficacy and minimizing the risk of adverse effects. Pharmacological monitoring of antiepileptic drugs is most beneficial during treatment initiation, after dose adjustments, in cases of suspected drug interactions or treatment failure, as well as in cases of overdose or the appearance of clinical signs of toxicity ⁵. Pharmacological monitoring of first-generation antiepileptic drugs, particularly phenobarbital (PB), carbamazepine (CBZ), and valproic acid (VPA), is already common practice in developed countries for adjusting dosages due to their narrow therapeutic margin and common neurological side effects ^5,6. Numerous studies have shown that plasma concentrations of antiepileptic drugs in some patients fall outside the therapeutic range, leading to treatment failure (due to underdosing) or toxicity (due to overdosing) ⁷. In Mali, therapeutic drug monitoring remains rarely used by clinicians due to its inaccessibility and cost, despite being recommended for most antiepileptic drugs currently used in clinical practice. Nowadays, plasma drug testing in general, and anti-epileptic drug testing in particular, cannot be performed in any of Mali's public hospitals. 

METHODOLOGY

This was a prospective descriptive study focusing on the therapeutic drug monitoring of three antiepileptic drugs in epilepsy patients treated at the Neurology Department of Point G University Hospital. The study was conducted over an eight-month. 

Data collection

The data were collected from survey forms that included information about the patient, their clinical and biological condition, dosage, and frequency of administration of the measured medication.

Parameters studied

We measured the residual concentrations of carbamazepine, valproic acid, and phenobarbital.

Sampling procedures

Blood samples were collected in EDTA tubes labeled with the patient's first and last name and the date of collection. Samples were taken in the morning, just before the new daily dose of treatment and after steady state had been reached. The samples were centrifuged at 3,000 rpm for 10 minutes and then stored at –20°C.

Analytical technique

The dosage of antiepileptic drugs (carbamazepine, valproic acid, and phenobarbital) was determined using the chemiluminescence immunoassay (CMIA) technique on an Abbott ARCHITECT i1000SR automated analyzer.

Therapeutic ranges

It range from 4 to 12 μg/mL; 50 to 100 μg/mL and 15 to 40 μg/mL for carbamazepine, valproic acid, and phenobarbital, respectively.

Ethical aspects

The Faculty of Pharmacy at the University of Science, Techniques and Technologies in Bamako approved the protocol. The anonymity and confidentiality of the information collected were preserved.

Data analysis

Data entry and analysis were performed using IBM SPSS Statistics version 22.0 software. Qualitative variables were expressed as percentages with numbers of subjects.

RESULTS

Sociodemographic and clinical characteristics of participants

The sociodemographic and clinical characteristics of participants are presented in Table 1. Males were the most represented gender, accounting for 57.50% of participants. 65% of participants were aged between 18 and 70 years. Generalised motor seizures were the most common (76.20%), followed by secondary generalised partial seizures (22.5%) and unspecified seizures or seizures with an unknown onset pattern (1.3%).

 

 

Table 1: Sociodemographic and clinical characteristics of participants

Characteristics		Effective	Percentage
Gender	Male	46	57.5
	Female	34	42.5
Age group	[2-12]	14	17.5
	[12-18]	11	13.8
	[18-70]	52	65
	70 and over	3	3
Types of seizures	Generalized motor seizures	61	76.2
	Focal seizures secondarily generalized	18	22.5
	Seizures with unknown onset	1	1.3

 

 

Frequency of anti-epileptic drug prescriptions and seizure progression

In most cases, anti-epileptic drugs were prescribed as monotherapy (78.80%). Carbamazepine was the most commonly prescribed drug (60.32%), followed by phenobarbital (20.63%) and valproic acid (19.05%). The combinations of antiepileptic drugs CBZ/PB and CBZ/VPA were observed in 47.06% and 29.41% of cases, respectively. Therapeutic compliance was good for 77.5% of participants. The progression of seizures was favorable in 74% of cases (Table 2).

 

 

Table 2: Frequency of anti-epileptic drug prescriptions, therapeutic compliance and seizure progression 

Treatment regimen	Molecules	Effective	Percentage
Monotherapy	Carbamazepine	38	47,5
	Phenobarbital	13	16,25
	Valproic acid	12	15
Dual therapy	Carbamazepine/ Phenobarbital	8	10
	Carbamazepine/ Valproic acid	5	6,25
	Valproic acid/ Phenobarbital	3	3,75
Triple therapy	Carbamazepine/Phenobarbital/ Valproic acid	1	1,25
Therapeutic compliance	Good	62	77.50
	Not good	18	22.50
Evolution of crises	Favorable	59	74
	Unfavorable	21	26

 

 

Plasma concentrations of antiepileptic drugs 

Among participants taking carbamazepine, 75% were receiving the normal dose, 2% were underdosed, and 23% were overdosed. 75% of participants taking phenobarbital were underdosed. Fifty percent of participants taking valproic acid were underdosed and 5% were overdosed (Figure 1).

Figure 1: Categories of plasma concentration of antiepileptic drugs

DISCUSSION

At the end of this study, we found that carbamazepine was the most commonly prescribed drug, followed by phenobarbital and valproic acid. These results are consistent with those of Eshiet et al., who found in their study in Nigeria that carbamazepine was the most commonly prescribed drug, with a frequency of 48.37% ⁸. However, our results differ from those reported by Gurshaw et al. in a study conducted in Ethiopia, where phenobarbital was the most commonly prescribed drug, followed by phenytoin and valproic acid ⁹. In India, a study showed that valproic acid was the most commonly prescribed antiepileptic drug, followed by phenytoin and carbamazepine. These differences could be explained by factors determining the choice of antiepileptic drug, such as age, gender, comorbidities, and type of seizures ¹⁰. In most cases, antiepileptic drugs were prescribed as monotherapy (78.8%). Our results disagree with those of a study on the use of antiepileptic drugs in India, which found that 19% of antiepileptic drugs were prescribed as monotherapy, 55% as dual therapy, and 26% as triple therapy. A study in Nigeria presented slightly similar results, with antiepileptic drugs being used as monotherapy in 54% of cases and as combination therapy in 46% of cases ^10,11. Some authors have reported that, in the management of epilepsy, combination therapy does not offer any significant advantage over monotherapy. It may increase the risk of drug interactions and could affect treatment compliance ¹². 

Our study showed that 75% of patients taking carbamazepine had plasma concentrations within the therapeutic range, while 23% had concentrations below this range. Grzesk et al. found similar results, with 71.0% of patients having plasma concentrations within the therapeutic range and 24.9% having concentrations below the therapeutic level ¹³. However, our results differ from those of Uskur et al. in Turkey, who reported that only 27.4% of patients achieved therapeutic levels¹⁴. 75% of patients taking phenobarbital had subtherapeutic plasma concentrations; only 25% of them had concentrations within the therapeutic range. Our results differ from those reported by Singh et al. in India, who found that 10% of the population studied had subtherapeutic concentrations and 30% had supratherapeutic concentrations. A study conducted in Iran by Babaei and Eslamai showed that 73% of patients receiving phenobarbital had plasma concentrations within the therapeutic range ¹⁵. Other authors have found similar results. They reported that 41% of patients taking valproic acid had normal plasma concentrations, 45% had lower concentrations, and 14% had higher than normal concentrations ⁵. However, the results observed by Ozunal et al. are different. Their study showed that 76.3% of patients receiving valproic acid had plasma concentrations within the therapeutic range; 19.9% had subtherapeutic concentrations and 3.8% had supratherapeutic concentrations ¹⁶. Poor treatment compliance was observed in 22.5% of patients. This result is comparable to that of other authors, who observed 24% of cases of non-compliance in China and 32% in Peru ^17,18.

CONCLUSION

Carbamazepine, phenobarbital, and valproic acid are widely used as first-line treatments in clinical practice in Mali. These molecules have shown significant pharmacokinetic variability. Further studies, particularly pharmacogenetic studies, are needed to better understand this pharmacokinetic variability in Mali.

Acknowledgement: The authors would like to thank the Dean of the Faculty of Pharmacy at the University of Science, Technology and Technology in Bamako. We are grateful to the team at the Neurology Department of Point G University Hospital. 

Competing Interests: The authors declare that they have no competing interests.

Author Contributions: All authors have equal contributions in the preparation of the manuscript and compilation.

Source of Support: Nil

Funding: The authors declared that this study has received no financial support.

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. 

Data Availability Statement: The data presented in this study are available on request from the corresponding author. 

Ethical approval: Not applicable.

REFERENCES 

1. Beghi, E. The Epidemiology of Epilepsy. Neuroepidemiology 2019;54:185-191. https://doi.org/10.1159/000503831 PMid:31852003 PMCid:PMC12038215

2. Tuchila, C. et al. Therapeutic Drug Monitoring and Methods of Quantitation for Carbamazepine. Journal of Mind and Medical Sciences 2017;4:100-114. https://doi.org/10.22543/7674.42.P100114

3. Sangare, M. et al. Epilepsy Research in Mali: A Pilot Pharmacokinetics Study on First-Line Antiepileptic Drug Treatment. J Epilepsy Res 2020;10:31-39. https://doi.org/10.14581/jer.20006 PMid:32983953 PMCid:PMC7494886

4. Singh, A. & Roy, V. Therapeutic Drug Monitoring (TDM) in Clinical Practice. Journal, Indian Academy of Clinical Medicine 2025;26:195.

5. Žigová, L., Göböová, M., Hrubá, O., Gažová, A. & Kosírová, S. Treatment stability of valproate, carbamazepine, and levetiracetam: a therapeutic drug monitoring study. Pharmacia 2025;72:1-7. https://doi.org/10.3897/pharmacia.72.e159728

6. Sommerfeld-Klatta, K., Zielińska-Psuja, B., Karaźniewcz-Łada, M. & Główka, F. K. New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs). Molecules 2020;25:5083. https://doi.org/10.3390/molecules25215083 PMid:33147810 PMCid:PMC7663638

7. Lim, S.-N. et al. Clinical impact of therapeutic drug monitoring for newer anti-seizure medications in patients with epilepsy: A real-world observation study. Biomedical Journal 2024;47:100680. https://doi.org/10.1016/j.bj.2023.100680 PMid:38036171 PMCid:PMC11402380

8. Eshiet, U. I., Ubaka, C. M. & Ukwe, C. V. Infrequent Monitoring of the Effects of Valproate and Carbamazepine Therapy in Patients With Epilepsy in Nigeria. J Cent Nerv Syst Dis 2020;12:1179573520925934. https://doi.org/10.1177/1179573520925934 PMid:32536783 PMCid:PMC7268118

9. Gurshaw, M., Agalu, A. & Chanie, T. Anti-epileptic drug utilization and treatment outcome among epileptic patients on follow-up in a resource poor setting. Journal of Young Pharmaceutics 2014;6:47. https://doi.org/10.5530/jyp.2014.3.8

10. Pal, A., Prusty, S. K., Sahu, P. K. & Swain, T. Drug utilization pattern of antiepileptic drugs: a pharmacoepidemiologic and pharmacovigilance study in a tertiary teaching hospital in India. Asian J Pharm Clin Res 2011;4:96-99.

11. Ejeliogu, E. U. & Uhunmwangho-Courage, A. Pattern of Adverse Drug Reaction to Antiepileptic Drugs at a Tertiary Hospital in North-Central Nigeria: A Prospective Observational Study. Journal of Advances in Medical and Pharmaceutical Sciences 2017;14:1-9. https://doi.org/10.9734/JAMPS/2017/35337

12. ArulKumaran, K. S. G., Palanisamy, S. & Rajasekaran, A. A study on drug use evaluation of anti-epileptics at a multispecialty tertiary care teaching hospital. Int J Pharm Tech Res 2009;1:1541-7.

13. Grześk, G. et al. Therapeutic drug monitoring of carbamazepine: A 20-year observational study. Journal of Clinical Medicine 2021;10:5396. https://doi.org/10.3390/jcm10225396

PMid:34830678 PMCid:PMC8621251

14. Uskur, T. & Güven, O. Therapeutic drug monitoring of carbamazepine and valproic acid: interindividual variability in epilepsy patients. Journal of Health Sciences and Medicine 2025;8:884-888. https://doi.org/10.32322/jhsm.1751139

15. Babaei, A. & Eslamai, M. H. Evaluation of therapeutic drug level monitoring of phenobarbital, phenytoin and carbamazepine in Iranian epileptic patients. International journal of clinical pharmacology and therapeutics 2007;45:121-125. https://doi.org/10.5414/CPP45121 PMid:17323792

16. Ozunal, Z. G. & İpek, B. O. Therapeutic Drug Monitoring Characteristics in a Tertiary University Hospital in 2019. Cureus 12, (2020). https://doi.org/10.7759/cureus.7612

17. Enríquez-Cáceres, M. & Soto-Santillana, M. Non-compliance with pharmacological treatment in patients with epilepsy. Revista de neurologia 2006;42:647-654. https://doi.org/10.33588/rn.4211.2005533 PMid:16736399

18. Wang, W. Z. et al. Efficacy assessment of phenobarbital in epilepsy: a large community-based intervention trial in rural China. The Lancet Neurology 2006;5:46-52. https://doi.org/10.1016/S1474-4422(05)70254-4 PMid:16361022