Thus, reduced doses may be used in renal and hepatic impairment.Its volume of distribution is around 306 L after oral administration and 203 L after parenteral administration. Chemistry
Tramadol is marketed as a racemic mixture of both R- and S-stereoisomers, because the two isomers complement each others analgesic activities. The (+)-isomer is predominantly active as an opiate with a higher affinity for the µ-opiate receptor (20 times higher affinity than the (-)-isomer). Synthesis and stereoisomerism
The chemical synthesis of tramadol is described in the literature. Tramadol [2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol] has two stereogenic centers at the cyclohexane ring. Thus, 2-(dimethylaminomethyl)-1-(3-methoxyphenyl)cyclohexanol may exist in four different configurational forms:

(1R,2R)-isomer
(1S,2S)-isomer
(1R,2S)-isomer
(1S,2R)-isomerThe synthetic pathway leads to the racemate (1:1 mixture) of (1R,2R)-isomer and the (1S,2S)-isomer as the main products. Minor amounts of the racemic mixture of the (1R,2S)-isomer and the (1S,2R)-isomer are formed as well. The isolation of the (1R,2R)-isomer and the (1S,2S)-isomer from the diastereomeric minor racemate [(1R,2S)-isomer and (1S,2R)-isomer] is realized by the recrystallization of the hydrochlorides. The drug tramadol is a racemate of the hydrochlorides of the (1R,2R)-(+)- and the (1S,2S)-(−)-enantiomers. The resolution of the racemate [(1R,2R)-(+)-isomer / (1S,2S)-(−)-isomer] was described employing (R)-(−)- or (S)-(+)-mandelic acid. This process does not find industrial application, since tramadol is used as a racemate, despite known different physiological effects of the (1R,2R)- and (1S,2S)-isomers, because the racemate showed higher analgesic activity than either enantiomer in animals and in humans.
Pregnancy and lactation
Tramadols use in pregnancy is generally avoided, as it may cause some reversible withdrawal effects in the newborn. A small prospective study in France found, while an increased risk of miscarriages existed, no major malformations were reported in the newborn. Its use during lactation is also generally advised against, but a small trial found that infants breastfed by mothers taking tramadol were exposed to about 2.88% of the dose the mothers were taking. No evidence of this dose harming the newborn was seen. Labor and delivery
Its use as an analgesic during labor is not advised due to its long onset of action (1 hour). The ratio of the mean concentration of the drug in the fetus compared to that of the mother when it is given intramuscularly for labor pains has been estimated to be 1:94. Children
Its use in children is generally advised against, although it may be done under the supervision of a specialist. On 21 September 2015, the FDA started investigating the safety of tramadol in use in persons under the age of 17. The investigation was initiated because some of these people have experienced slowed or difficult breathing. The FDA lists age under 12 years old as a contraindication. Elderly
The risk of opioid-related adverse effects such as respiratory depression, falls, cognitive impairment and sedation is increased. Tramadol may interact with other medications and increase the risk for adverse events.