Need of new Homeopathic drug and dose development

Dr Puneet Kumar Misra

Introduction – when a person in the morbid state and its first needs are the treatment, and the priority of the clinicians are    the selection of drug   along with its sufficient dose and administration.  The sufficient dose and its administration methods   are developed by the serial process of drug development. 

Organon of Medicine by Samuel Hahnemann

121- 140 mode of proceeding when we make trial of them or other persons  > (122- In proving medicines to ascertain their effects on the healthy body, it must be borne in mind that the strong, heroic substances, as they are termed ,are liable even in small dose to produce changes in the health even of  robust person .those of milder power must be given for these experiments in more considerable quantities; in order to observe the action of very weakest, however, the subject of experiment should be person free from disease ,and who are delicate ,irritable and sensitive.

275-287strength of the doses for homoeopathic use – how it may be increased or diminished .their dynamization. (278 aphorism organon of medicine  “ here the question arises ,what is this most suitable degree of minuteness for sure and gentle remedial effect ;how small ,in other words, must be the dose of each individual medicine, homeopathically selected for  a case of disease ,to effect the best cure ? to solve this problem, and to determine for every particular medicine ,what dose of it will suffice for homoeopathic therapeutic purpose and yet be so  minute that the gentlest and most rapid cure may be thereby obtained – to solve this problem is, as may easily be conceived ,not the work of  theoretical speculation; not by fine-spun reasoning, not by specious sophistry, can we expect to obtain the solution of this problem.[ ‘it is just as impossible as to tabulate in advance all imaginable cases’ in the sixth edition] pure experiment ,careful observation[ ‘of the sensitiveness of each patient’ in the sixth edition]   . and accurate experience can alone determine this; and  it were absurd to adduce the large dose of unsuitable (allopathic) medicine of the old system ,which do not touch the diseases side of the organism homeopathically ,but only attack the parts unaffected by the diseases ,in opposition to what pure experience pronounces respecting the smallness of the doses required for homoeopathic cures.) 

Drug (French: Drogue—a dry herb)
A) It is the single active chemical entity present in a medicine that is used for diagnosis, prevention, treatment/ cure of a disease. This disease oriented definition of drug does not include contraceptives or use of drugs for improvement of health. 

B) The WHO (1966) has given a more comprehensive definition—“Drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient.” 

The Source of drugs in the homoeopathy is from animal kingdom, plant kingdom, mineral kingdom. Sarcode, nosode , imponderabilia, and details of the all drugs regarding its action and symtomatologyare details in the maetriamedica,and source of the materia medica in the homoeopathy are– 1) empirical source,2) experiment on plant ,3)experiment on animal 4) chemical source 5) toxicological source 6) accidental source, 7) clinical observation 8) laboratory experiments, 9) doctrine of signature 10) human provings .

PRINCIPLES OF DOSE SELECTION– The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug, in controlled clinical trials or in post marketing use, defines the relationships between dose or plasma concentration and these dual effects and has important implications for initiation of drug therapy:

DRUG DOSAGE‘Dose’ is the appropriate amount of a drug needed to produce a certain degree of response in a given patient. Accordingly, dose of a drug has to be qualified in terms of the chosen response. The dose of a drug is governed by its inherent potency, i.e. the concentration at which it should be present at the target site, and its pharmacokinetic characteristics. The recommended doses are based on population data and cater to an ‘average’ patient. However, individual patients may not be ‘average’ in respect to a number of pharmacokinetic and pharmacodynamic parameters, emphasizing the need for individualizing drug dose. 

Maximum dose –it is the largest or maximum possible amount of a medicine, which can be taken at a time by an adult not endangering his life.

Minimum dose – it is that amount of medicine, though in the smallest possible quantity, that can produce a gentle remedial effect and the least possible excitation of the vital force, and yet is sufficient to effect the necessary change in it.   

Fatal or lethal dose – the amount of such a dose is usually toxicological or narcotic, which can even cause death to living organism .the fatal dose of different substance vary which depend upon their respective toxicity .a fatal dose of a milder narcotic or poison will obviously be less than of a stronger narcotic or poison.

Booster dose – a dose administered subsequently to enhance the action of the initial dose.

Fractional or refractive or divided dose – it is the fraction of a full dose which is to be taken at short intervals.

Physiological dose – A dose which stimulates the normal physiology or function of various system or organ of our body. The symptoms thus appearing are known as physiological symptoms. 

Standard dose The same dose is appropriate for most patients—individual variations are minor or the drug has a wide safety margin so that a large enough dose can be given to cover them.

Regulated dose The drug modifies a finely regulated body function which can be easily Measured. The dosage is accurately adjusted by repeated measurement of the affected physiological parameter and  measurement of plasma drug concentration is not needed.

Target level dose – The response is not easily measurable but has been demonstrated to be obtained at a certain range of drug concentration in plasma. An empirical dose aimed at attaining the target level is given in the beginning and adjustments are made later by actual monitoring of plasma concentrations. When facilities for drug level monitoring are not available, crude adjustments are made by observing the patient at relatively long intervals.

Titrated dose – The dose needed to produce maximal therapeutic effect   cannot be given

Because of intolerable adverse effects. Optimal dose is arrived at by titrating it with an acceptable level of adverse effect. Low initial dose and upward titration (in most non-critical situations) or high initial dose and downward titration (in critical situations) can be practised. Often a compromise between sub maximal therapeutic effect but tolerable side effects can be struck.

Loading dose  This is a single or few quickly repeated doses given in the beginning to attain target concentration rapidly.  

Maintenance dose –   This dose is one that is to be repeated at specified intervals after the attainment of target Cpss(steady state plasma concentration) so as to maintain the same by balancing elimination.  However, if there is no urgency, maintenance doses can be given from the beginning. 

The concept of loading and maintenance dose is valid also for short t½ (plasma half life)  drugs and i.v. administration in critically ill patients and  followed by slow i.v. infusion or intermittent fractional dosing.

Curative dose – a dose sufficient to restore normal health 

Stages in New Drug Development

  • Synthesis/isolation of the compound: (1–2 years)
  • Preclinical studies: screening, evaluation, pharmacokinetic and short-term toxicity testing in animals: (2–4 years)
  • Scrutiny and grant of permission for clinical trials: (3–6 months)
  • Pharmaceutical formulation, standardization of chemical/biological/immuno-assay of the compound: (0.5–1 year)
  • Clinical studies: phase I, phase II, phase III trials; long-term animal toxicity testing: (3–10 years)
  • Review and grant of marketing permission: (0.5–2 years)
  • Post marketing surveillance: (phase IV studies)

Clinical Development of New Drugs

Phase I

Healthy volunteers (20–80) These involve initial single-dose, ‘first-into-man’ studies, followed by repeated-dose studies. They aim to establish the basic pharmacokinetic and pharmacodynamic properties, and short-term safety

• Duration: 6–12 months

Phase II

Patients (100–200) These investigate clinical effectiveness (‘proof of concept’), safety and dose–response relationship, often with a surrogate clinical endpoint, in the target patient group to determine the optimal dosing regimen for larger confirmatory studies

• Duration: 1–2 years

Phase III

Patients (100s–1000s) These are large, expensive clinical trials that confirm safety and efficacy in the target patient population, using relevant clinical endpoints. They may be placebo-controlled studies or comparisons with other active compounds.

• Duration: 1–2 years

Phase IV

Patients (100s–1000s) These are undertaken after the medicine has been marketed for its first indication to evaluate new indications, new doses or formulations, long-term safety or cost-effectiveness. 

Discussion and Conclusion

1) The phase 1st of clinical development of new drugs in the modern medicine is alike as the proving on Healthy volunteers as describe in the aphorism 122 of “organon of medicine “ , but  in the modern medicine this study are used to establish the basic pharmacokinetic and pharmacodynamic properties of drug and short-term safety of  person, but in the homoeopathy this study data are used in the treatment of diseases  on the basis of symptoms similarities of diseases found during proving .

2)The 2nd & 3rd phase  of clinical development of new drugs in the modern  medicine are  used for the establish of  clinical effectiveness (‘proof of concept’)  and  its efficacy on the patient and using relevant clinical endpoints, and 4th  stage for its first indication to evaluate new indications, new doses or formulations on the patients  after detail observations . 

3) In the homoeopathy 2nd, 3rd, and 4th stage are not marked, but various clinical observations proves it on the basis of symptoms similarities diseases  .

4) The aphorism 278 partial support the need of establishment of the 2nd, 3rd, and 4th stage of the drug development in the homoeopathy 

5) The minimum maximum and lethal dose concept describe in the short in the aphorism 275 – “but likewise on the proper size or rather smallness, of the dose .if we give too strong a dose of a medicine which may have been even quite homeopathically chosen for the morbid state before us, it must ,notwithstanding the inherent beneficial character of its nature, prove injurious by its mere magnitude, and in the  aphorism 275 proper size means  maybe  (minimum, Standard, maximum) and smallness means minimum dose ,and  too strong dose indication of   the Fatal or lethal dose.

6) Maintenance dose(This dose is one that is to be repeated at specified intervals after the attainment of target Cpss (steady state plasma concentration)  so as to maintain the same by balancing elimination) Loading dose(This is a single or few quickly repeated doses given in the beginning to attain target concentration rapidly) Titrated dose(Low initial dose and upward titration (in most non-critical situations) or high initial dose and downward titration (in critical situations) can be practised) ,Target level dose(obtained at a certain range of drug concentration in plasma) .the all mentioned  dose need repeated manner and in the organon of medicine also describe the provision of repeats in the aphorism 248

7)The  various materia madica also supported the repeated administration   of the drugs      for example WILLIAM BOERICKE, M.D, ACONITUM NAPELLUS Must be repeated frequently in acute diseases, BELLADONNA -First to thirtieth potency and higher. Must be repeated frequently in acute diseases.

8)  The dose in the modern medicine   means only the quantity (amount ) of drug for apply , and in homoeopathy   the dose means quality(potency ) and quantity(amount ) selection of drug and both is important issue for treatment but here lacking  of  proper guidance because the drug description in the various manners in various materia madica for example ( a) materia medica of proving b) physiological materia medica c) clinical materia medica d) comparative materia medica e) therapeutic  materia medica f) descriptive materia medica g) expressive picture type of materia medica)  .  

9) it is demands of current situation of treatments, that we reveal the findings of all drugs available  in the different  materia madica mentioned above with  the support of the modern tools of investigation and collect  the data of drugs from the prescribing approach of clinicians in the various territory, developed  the new homoeopathic materia madica on the basis of basic pharmacokinetic and pharmacodynamic properties of the drugs and this process is easily possible through the help of social media in the present time. 

Reference 

  1. Davidson Principal & Practice of medicine 23nd Edition
  2. Augmented Textbook of Homoeopathic Pharmacy 2nd Edition D D Banerjee’s ,  
  3. A Text book of Homoeopathic Pharmacy Mandal & Mandal 
  4. Essentials of Medical Pharmacology Seventh Edition KD TRIPATHI MD
  5. Organon of Medicine by Samuel Hahnemann combined 5th & 6th editions      translated by Dr R E dudgeon & Dr W Boericke 
  6. Harrison’s Principles of Internal Medicine, 19 Edition 
  7. Scholar’s manual of homoeopathic materia medica dr azad rai first edition 2005
  8. GEMS text book of homoeopathic materia medica dr j.d.patil 

Dr Puneet Kumar Misra
B.Sc, BHMS
Lecturer (Practice of Medicine)
Govt Pt J LN H M C  Kanpur

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