5. General Comment On Drug Half-Life

If the frequency of taking a capsule/tablet (say 12 hours) is much shorter than the drug half life (say 24 hours), the capsule/tablet may be eliminated at something like three times the period of the half-life to reduce the average drug level slowly. The residual drug from the other capsules/tablets sustains the background level. If the frequency of elimination of a capsule/tablet is more than five times the half life, it will fall temporarily but then build back to its previous level.

For short half-life drugs taken twice or three times per day the drug reduction needs to be achieved in fractions of tablets with a consolidation period in between. The concentration in the body does not float down but reduces more rapidly according to the intake. Therefore the reduction here will need to be in small increments as the body levels fall so quickly. The greater the dependency the longer the consolidation will be needed between step changes in dosage and the smaller the size of the reduction acceptable.

A given drug will have an inherent half-life range in the body. To achieve a longer half-life various techniques may be adopted. It is possible to have coatings on capsules/particles within capsules where the inner ones dissolve later and therefore release their drug more slowly.

Some drug particles are coated to slow down dissolution in the body. Double and triple coatings will give slower dissolution rates. However this technique can only be applied for as long as it takes the drug to pass through the body. If a longer half-life is required, a chemical intermediary can be used. Here the entire dose will be released into the blood stream but part of it will be in the form of a related drug which breaks down into the required drug over a period of several days. This can allow longer half lives to be achieved.

Antidepressant Half Life Information

 

					Sep-01
drug	generic name	company	type	max mg/day	Half life, hrs
Anafranil	clomipramine	Novartis	TCAD	250	21(19-37)
Asendis	amoxapine	Wyeth	TCAD	300	no info
Cipramil		Lundbeck	SSRI	60	36 (28 - 42)
	Elderly patients may metabolise more slowly and need lower dose
Edronax		Pharmacia	SNRI	12	8
Efexor	venlafaxine	Wyeth	SSNRI	375	5 (5 to 11)
"    XL		Wyeth	SSNRI	225	20 to 22
Faverin		Solvay	SSRI	300	21
Lentizol	amitriptyline hyd.	Pfizer		200	15 (10 - 28)
	Nortriptyline, the most important metabolite, has a half-life of 36 hours (18-60 hours).
	It has a polymorphically controlled metabolism (debrisoquine metabolism). In subjects
	with a slow metabolism (in Switzerland about 9% of the population) high therapeutic
	doses can lead to toxic plasma levels very quickly.
Lustral,	sertraline	Pfizer	SSRI	200	26 (22 to 33)
Prothiaden	dothiepin hyd.	Knoll	TCAD	150	19 to 33
Prozac	fluoxetine	Dista	SSRI		7 to 9 DAYS
	Approx. 7% of people have difficulty metabolising fluoxetine and it then increases rapidly
Seroxat	paroxetine	GSK	SSRI	50	21 to 26
Sinequan	doxepin	Pfizer	TCAD	100x3 p.d.	28 to 52
Surmontil	trimipramine	Futuna	TCAD	300	24
Tofranil	imipramine	Novartis	TCAD	200	19
	Elderly shown to have slower metabolism giving half life of 28 hours.
	Young me shown to have higher metabolism giving half life of 16 hours.
Triptafen	phenothiazine	Goldshield	TCAD	4 tabs daily	30
Zispin	mirtazapine	Organon	N&S enhancer	45	20 to 40

 

 

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