Need for therapeutic drug monitoring of Ayurveda medicines, therapy, and probable executable plans

Ayurveda has rich wisdom in medicine, pathophysiology, medical ethics, pharmacology, and therapeutic drug monitoring (TDM). The TDM is a branch of medicine that deals with optimizing individual dosage regimens by measuring drug concentration in a patient’s blood at specific intervals.[1] TDM is essential to ensure safe and effective use of the drug and to avoid dose as well as drug interaction-related adverse drug events. As the safe use of medicine depends on the quality of the raw materials, manufacturing process, packaging, prescribed dosage, and careful dispensing, the implementation of an effective TDM typically requires consideration of several factors, such as assessing raw drug quality, expertise of the pharmacist, knowledge of the physician, well equipped clinical laboratory, and standard dispensing unit with personnel having enough expertise in clinical pharmacokinetics.[2] Several guidelines related to such factors are finely narrated in the classical text of Ayurveda. The description of Rasashala (pharmacy) covers the aspects of raw manufacturing, storage, equipment, and dispensing. The core qualities of physician, drug/medicine, and assistant/nurse/pharmacist in case of drug dispensing are highlighted under the description of qualities of Bhishaka, Dravya, and Upasthata, respectively. In other words, in its way, TDM was well followed by Ayurveda. With the scientific and technological advancement in health sciences, the precision in patient care, and systematic approach to monitor therapy has increased significantly. It is imperative for systems, such as Ayurveda, to create strategies and incorporate current practices, like TDM, to adhere to the contemporary regulatory demands, to fulfill the knowledge gap, and to move towards advanced, evidence-based practices. Thus, in view of the development in information technologies, analytical advancements related to drug monitoring, clinical pharmacology, and laboratory technologies, the Ayurveda approach of TDM needs to be revised. Need for TDM in Ayurveda As mentioned before, for TDM, measuring the drug concentration in an individual’s blood is an essential step. Such a concentration can be measured based on the identification of the specific active compound administered through the drug. In other words, the chemical information of active compounds is necessary. However, Ayurveda herbs contain a large number of active phytoconstituents, and Ayurveda formulations are complex mixtures of multiple ingredients, including metals/minerals. Thus, contemporary knowledge and analytical methods have limitations while interpreting the pharmacokinetics of Ayurveda formulation. Due to such limitations, generative evidence that supports the efficacy and mode of action of Ayurveda formulations is need of hour. Unlike symptomatic and laboratory-based assessment parameters, the Ayurveda treatment approach is individual-tailored (Prakriti, Agni, Koshtha, Satmya, Dhatu Sarata, etc.), and the pathological aspect (Vyadhi Samprapti) is unassessable through laboratory investigations; indicating a need of categorized TDM for a formulation based on Ayurveda individualized point of view. For example the therapeutic dose of Sameerpannaga Rasa may vary in Vata, Pitta, and Kapha Prakriti individuals. The dose of Sameerpannaga Rasa tolerable in Kapha Prakriti can cause adverse drug reactions (ADR) in Pitta Prakriti individuals. In view of widespread concerns of the safety of Ayurveda formulation and the importance of TDM in ensuring safety, TDM should be implemented in Ayurveda academics, research, and practice. Information on bioavailability and plasma half-life profile of a drug are major factors in deciding dose and frequency of dosage. Administration of dose levels that exceed the dose level required to achieve specific bioavailability leads to excretion of the exceeded drug concentration or may cause ADR.[3] On the other hand, a dose level less than the required level to reach adequate bioavailability may lack therapeutic effect.[4] Similarly, the plasma half-life profile of a drug needs to be taken into account to decide the interval between two dosages.[5] The administration of the drug before the plasma drug concentration reaches half can be similar to an overdose. At the same time, non-administration of a drug, even after the plasma drug concentration drops below half, may reduce the therapeutic effect. As information on the pharmacokinetics and pharmacodynamics of Ayurveda formulations is currently lacking, to ensure patient safety, it is crucial to focus on TDM. Challenges in Implementing TDM The manifestation of a disease is a complex process that mostly involves impairment in several physiological functions/organs. Thus, a combined drug approach (use of more than one formulation) is preferred for treatment. In modern medicine, the interactions between drugs, contraindications, and drug-food interactions are clearly articulated, which has resulted in simplicity TDM. On the other hand, there exists variability in the same Ayurveda formulations based on classical reference, raw drug quality, and preparation method leading to variation in drug action, safety, and efficacy. Moreover, the lack of clear guidelines for combining specific formulations to treat a particular disease is prompting the development of numerous, often unregulated, combinations. For effective implementation of TDM, managing the variability in formulations and their combinations is very challenging. Different approaches in treatment may also arise based on the interpretation of the involved Dosha, Samprapti of the disease, Nidana Panchaka, physician experience, available/frequently utilized drugs/formulations, and lastly, diagnostic findings from the patient's clinical assessment. Such factors may cause multiple obstacles in elucidating drug pharmacokinetics and pharmacodynamics, and thereby TDM. The use of different dosage forms or dosage form preparation methods for a few formulations is also a challenging issue for TDM. Vasa Swarasa can be prepared by the Putapaka method, extractions from pulverized Kalka, or Swedana method; the use of branded Vasa Kwath or Vasavaleha instead of Swarasa are examples of differences in dosage form and method of preparation. Commonly, Ayurveda is well-known for herbal remedies and health supplements, and thus, most Ayurveda formulations can be purchased over the counter without a prescription from an Ayurveda expert. These formulations are not limited to health supplements but also include treatments for various ailments. However, when an ADR is reported, the blame is often placed on Ayurveda itself and not on the manufacturer or consumer. There should be clear guidelines regarding which formulations can be sold over-the-counter and for which formulations a prescription from an Ayurveda expert should be made mandatory; this is necessary to limit self-medication as common people are mostly not aware enough of factors to be considered while deciding a formulation and method of its administration. Opportunities in TDM There is significant scope for innovative research in the field of TDM. The application of advanced analytical technologies to harness the potential of Ayurveda therapies can bring significant insight into the mode of action of Ayurveda formulations as well as the interaction between formulations. Discovering the administration, distribution, metabolism, and elimination (ADME) of Ayurveda formulation is an essential step for TDM. There is huge scope for developing guidelines and categorisation of dosage in relation to age and various types of Prakriti. Research in clinical settings for TDM of formulations containing metals, minerals, and scheduled drugs can open new opportunities for collaborative research and can greatly contribute to generating evidence-based TDM. Also, in view of various Pharmaceutical manufacturing techniques narrated in different classical texts of Ayurveda, TDM research can be undertaken to evaluate changes in pharmacokinetics based on changes in chemical composition due to specific drug preparation methods. Similarly, there are descriptions in Ayurveda text where specific Anupana is given for a specific formulation, or specific Pathya is advised while administering a formulation; the significance of such classical concepts needs to be explored on clinical grounds as they are definitely related to TDM. Probable Executable Plans and Recommendations The modern concept of TDM is well-established but has limitations when applied to Ayurveda. It is requireed to create robust strategies for systematic and effective implementation of TDM in Ayurveda. A few of the probable executable plans are summarized below. a) Developing a standardized monitoring process based on Ayurveda and modern concepts. b) Systematic and insightful summarization and generalization of ADR-related data received annually. c) Undertaking TDM-focused collaborative research initiatives with competent research organizations to establish pharmacokinetics and pharmacodynamics of Ayurveda herbs and formulations while contemplating Anupana, processing methods, and Prakriti. d) Creating a central database for phase 4 clinical trials (post-market surveillance) and annual publication of its summarized report. e) As a prerequisite for safety, ensuring and maintaining transparency in standard manufacturing procedure and standard operating procedure. f) Organizing integrative trainings/workshops/symposiums and education programs on TDM pertaining to Ayurveda interventions. g) Establishing guidelines for over-the-counter purchase of Ayurveda medicines. Conclusion Integrating TDM into Ayurveda offers a promising avenue to enhance patient safety and treatment effectiveness. However, the intricate nature of Ayurvedic formulations calls for research to provide pharmacokinetic and pharmacodynamic data that ensure their safety and efficacy. Establishing standardized guidelines will enhance quality and therapeutic outcomes, reducing the risk of ADRs. Regulatory and ethical concerns surrounding Ayurvedic products necessitate stricter oversight, including mandatory prescriptions for specific items to protect public health. The TDM field presents opportunities for innovative research, especially in understanding the ADME of these formulations. Collaborative research can create new guidelines that merge traditional wisdom with modern science. To successfully implement TDM in Ayurveda, it is vital to develop standardized monitoring processes, establish a centralized post-market surveillance database, and initiate educational programs for practitioners. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.