Modafinil, also known as Provigil, is a drug to improve wakefulness, especially to adult’s that experience excessive sleepiness. The excessive sleepiness that adults experience is usually the result of a condition called obstructive sleep apnoea, narcolepsy or shift work sleep disorder.
It was 1998 when the Food and Drug Administration (FDA) first approved the use of Modafinil for treatment of narcolepsy. The FDA then approved the use of modafinil for obstructive sleep apnoea and shift work sleep disorder. One Modafinil tablet typically contains either 100mg or 200mg of Modafinil, following that are inactive ingredients including lactose monohydrate, croscarmellose sodium, povidone, microcrystalline cellulose, magnesium stearate and pregelatinized starch.
The chief metabolite of Modafinil is modafinil acid, with modafinil sulfone as the other major metabolite. Modafinil acid and modafinil sulfone are both inactive in modafinil, without any appearance of contribution to the stimulant or wakefulness effect of the drug.
During modafinil’s breakdown process, it is primarily hydrolyzed by either an amidase or esterase enzyme turning it into modafinil acid. It is hypothesized that metabolism can increase the clearance and polarity of modafinil that there is a significant clearance of modafinil acid in the drug.
Pharmacokinetic Properties of Modafinil
A racemic compound, modafinil’s enantiomers have varying pharmacokinetics that it has three times elimination of t1/2 of R-isomer than the S-isomer in adult humans. Here are some important pharmacokinetic properties of the drug:
Absorption – The body absorbs modafinil well with a peak plasma concentration that reaches about 2 to 4 hours after the drug is administered. The bioavailability of the drug is not at all affected by food. However, if it is taken with food the absorption or tmax might be delayed for about an hour.
Biotransformation – The liver metabolizes modafinil. Its chief metabolite is modafinil acid, taking 40 to 50% of every modafinil does and has no pharmacological activity.
Elimination – Excretion of the medication as well as its metabolites are mainly renal. There is a small part of the drug being eliminated that remains unchanged. It takes about 15 hours for the effective elimination of modafinil’s half-life.
Distribution – When taken, modafinil moderately bounds itself (about 60%) to plasma protein. The medication primarily binds to albumin, indicating a low risk of interaction that of strongly-bound drugs.
Linearity or Non-Linearity – Modafinil has time-independent and linear pharmacokinetic properties. Its systemic exposure rises in a dose with proportional manner more than 200-600mg range.
The elderly, mainly patients over 65 years old, are advised to commence modafinil therapy at 100mg every day. For the pediatric population, mainly patients 6-7 years old, the half-life is about 7 hours, increasing in age until the half-life values reach those of adults.
Safety Data of Modafinil
Toxicology of the drug shows that single or repeated use of Modafinil offers no specific toxic action to any animal. It is not considered carcinogenic or mutagenic. In reproductive toxicity studies of modafinil that were conducted in rabbits and rats, it showed that the skeletal variations have increased incidence.
There is also increased the incidence of embryo-fetal lethality and several evidence of the increase of stillbirths, although only in rats. There were no signs that Modafinil has an effect on fertility and there is no evidence of any teratogenic potential in exposures that are equivalent to the maximum Modafinil dose in humans.