Tilidine is metabolised to 90% and eliminated renally. The rest appears in the faeces. Depending on the extent of the impairment, the maximum concentration of nortilidine in plasma is lower in liver function than in healthy individuals and the half-life is prolonged. In case of severe hepatic insufficiency the therapy is questionable. In these cases, it is possible that the formation of active nortilidine may be so low that the analgesic effect is insufficient. In addition, in the combination preparations with naloxone, the inactivation of the same can only be insufficient. The consequent antagonisation of the nortilidine effect can lead to a further loss of activity. It is manufactured by a Diels-Alder reaction of 1-"N","N"-dimethylaminobuta-1,3-diene with ethyl atropate, yielding a mixture of isomers, of which only the ("E")-("trans")-isomers are active and are separated subsequently from the mixture by precipitation of the inactive ("Z")-("cis")-isomers as zinc complex. The inactive ("Z")-("cis")-isomers may be epimerised to the more thermodynamically favoured ("E")-("trans")-isomers via reflux in diluted phosphoric acid. Turkish ney  The Turkish ney is an end-blown reed flute, an Ottoman variation on the ancient ney. Together with the Turkish tanbur lute and Turkish kemençe fiddle are considered the most typical instruments of Classical Turkish music. The ney also plays a primary role in the music of the Mevlevi Sufi rites ("semâ"). A rim-blown, oblique flute made of giant reed ("Arundo donax"), the Turkish ney has six finger-holes on the front and a high-set thumb-hole on the back. The thumb hole is not centered, but rather is angled to the left or right depending on whether the instrument was intended to be played with the left or right hand on top. A feature that distinguishes it from similar instruments of other cultures is the flared mouthpiece or lip-rest, called a "bashpare", traditionally made of water buffalo horn, ivory, or ebony, but in modern times many are plastic or similar durable material. The Turkish ney is played by pressing the "bashpare" against nearly-closed lips and angling the flute so that a narrow air-stream can be blown from the center of the lips against the interior edge to the left or right, depending on whether the flute is left- or right-handed in construction.