Methamphetamine excretion

Methamphetamine - Methamphetamine is rapidly absorbed from the Gl tract. The primary site of metabolism is in the liver. The biological half-life is in the range of 4 to 5 hours. Excretion occurs in the urine and is dependent on urine pH. Alkaline urine increases the drug half-life. 

Pharmacokinetics Rapidly absorbed from the G1 tract. Crosses the blood-brain barrier. Metabolized in the liver to the active metabolites. Primarily excreted in urine. Half-life 17hr (amphetamine), 20 hr (methamphetamine). 

Methamphetamine passes the blood-brain barrier better than amphetamine, and there is evidence that chronic use of methamphetamine can result in permanent damage to dopamine neurons. Both pass the placental barrier, and there is some evidence that abuse by a pregnant woman can result in fetal abnormalities. Methamphetamine is found in breast milk. The half-life of methamphetamine and amphetamine is about 10 to 13 hours. Some methamphetamine is metabolized to amphetamine, and amphetamine-glucuronide can be detected in urine for about two days. About 50% of methamphetamine is excreted unchanged in the urine over two to three days. 

In humans, both the d- and L-forms undergo hydroxylation and A-demethylation to their respective />hy dr ox y me thainphetamine and amphetamine metabolites. Amphetamine is the major active metabolite of methamphetamine. Under normal conditions, up to 43% of a D-methamphet-amine dose is excreted unchanged in the urine in the first 24 h and 4 to 7% will be present as amphetamine. In acidic urine, up to 76% is present as parent drug10 compared with 2% under alkaline conditions. Approximately 15% of the dose was present as /7-hydroxymethamphetamine and the remaining minor metabolites were similar to those found after amphetamine administration. Urine concentrations of methamphetamine are typically 0.5 to 4 mg/L after an oral dose of 10 mg. However, methamphetamine and amphetamine urine concentrations vary widely among abusers. Lebish et al.11 reported urine methamphetamine concentrations of 24 to 333 mg/L and amphetamine concentrations of 1 to 90 mg/L in the urine of methamphetamine abusers. 

Oyler, J.M., Cone, E.J., Joseph, R.E., Moolchan, E.T., and Huestis, M.A., Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans, Clin. Chem., 48(10), 1703-1714, 2002. 

Nakahara, Y., Takahashi, K., and Konuma, K., Hair analysis for drugs of abuse. VI. The excretion of methoxphenamine and methamphetamine into beards of human subjects. Forensic Sci. Int., 63, 109,1993. 

The GC/MS procedures for methamphetamine are described in Table 4. The papers published in Japanese - have corresponding reports in English. - - Methamphetamine was detected and determined by mass fragmentography in rat hair after administration of the substance. Nine methods also detected the metabolite amphetamine or amphetamine alone. Suzuki et al. determined methamphetamine also in nail, sweat and saliva. The workup (EX after acid or alkaline hydrolysis) and derivatization technique (methanol-trifluoroacetic acid [TEA]) is rather uniform in most procedures. Nakahara et al. ° used methoxyphenamine excretion into beard hair to discuss several washing procedures. Alkaline or methanolic extraction are used with one exception. Derivatization is mainly made by fluorinated anhydrides. A review ° gives details on analytical procedures, incorporation rates of amphetamines from blood to hair, and relationship between drug history and drug distribution in hair. 

The metabolism of methamphetamine (11) involves both N-demethylation and ring hy-droxylation. Caldwell et al. (61) reported that 23% of the administered dose was excreted as unchanged drug, 18% as the 4-hydroxylated compound, and 14% as the N-demethylated amphetamine. 

Fitzgerald RL, Ramos JM Jr, Bogema SC, Poklis A. Resolution of methamphetamine stereoisomers in urine drug testing Urinary excretion of R( )-methamphetamine following use of nasal inhalers. J Anal Toxicol 1988 12 255-9. 

Urinary excretion data of human subjects indicate that 4-hydroxylation of methamphetamine is much more extensive than that of amphetamine the metabolic ratio (total hydroxymethamphetamine/methamphetamine) in urine averaged about 15 with individual variations of approximately fiftyfold (Shimosato 1988), suggesting considerable importance of CYP2D6 polymorphism in the fate of methamphetamine. On the other hand, there seems to be no information on the further metabolism of p-hydroxymethamphetamine as is available for p-hydroxyamphetamine. 

Shimosato, K. Urinary excretion of p-hydroxylated methamphetamine metabolites in man. II. Effect of alcohol intake on methamphetamine metabolism. Pharmacol Biochem Behav 29 733-740, 1988. 

PO. Well absorbed, enters CNS, excreted without undergoing metabolism, half-life = 4-6 hrs. Elimination is slowed by alkalination of urine. Often abused. Severe tolerance and dependence. Methamphetamine ( Speed") acts similarly, but is very addictive and often abused. MAO inhibitors hypertensive crisis, CNS overstimulation. Barbiturates supraadditive mood elevation. Tricyclic Antidepressants potentiate CNS stimulation, inhibit metabolism of amphetamine. Overdose treatment Acidify urine. Give chlorpromazine to treat CNS symptoms and alpha-receptor blocker to lower blood pressure. 

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