Morphine bioavailability

Kaiko RF, Lazarus H, Cronin C, Grandy R, Thomas G, Goldenheim P, Controlled-release morphine bioavailability (MS Contin tablets) in the presence and absence of food. Hosp J (1990) 6, 17-30. 

De Conno F, Ripamonti C, Bianchi M, Ventafridda V, Panerai AE. Diclofenac does not modify morphine bioavailability in cancer patients. Pain (1992) 48, 401-2. 

The opium alkaloid morphine is representative for this group of opiates and also for other opioid analgesics. Morphine is a full agonist for both the jx and the k receptors. It is used to relieve severe acute pain, or chronic pain in terminally ill patients. Its oral bioavailability varies from 15% to 35% and its... 

Like morphine, codeine is a naturally occurring opioid found in the poppy plant. Codeine is indicated for the treatment of mild to moderate pain and for its antitussive effects. It is widely used as an opioid antitussive because at antitussive doses it has few side effects and has excellent oral bioavailability. Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect It is one of the most commonly used opioids in combination with nonopioids for the relief of pain. The administration of 30 mg of codeine in combination with aspirin is equivalent in analgesic effect to the administration of 65 mg of codeine. The combination of the drugs has the advantage of reducing the... 

Hydromorphone is eight times as potent as morphine but has less bioavailability following oral administration. Its side effects do not differ from those of morphine but are more intense. Hydromorphone is indicated for use in severe pain and in high doses for relief of pain in opioid-addicted patients. 

A drug such as morphine is almost completely absorbed (f = 1), so that loss in the gut is negligible. Flowever, the hepatic extraction ratio for morphine is 0.67, so (1 - ER) is 0.33. The bioavailability of morphine is therefore expected to be about 33%, which is close to the observed value (Table 3-1). 

Methadone has undergone a dramatic revival as a potent and clinically useful analgesic. It can be administered by the oral, intravenous, subcutaneous, spinal, and rectal routes. It is well absorbed from the gastrointestinal tract and its bioavailability far exceeds that of oral morphine. 

Methadone Slow-acting agonist of M-opioid receptor Acute effects similar to morphine (see text) Substitution therapy for opioid addicts High oral bioavailability half-life highly variable among individuals (range 4-130 h) Toxicity Respiratory depression, constipation, miosis, tolerance, dependence, and withdrawal symptoms... 

Pharmacokinetic properties Codeine (Sindrup and Brosen, 1995) has a good oral bioavailability. The compound is extensively metabolized by O- and N-demethylation followed by glucuronidation. The main metabolites are norcodeine, morphine and hydrocodeine and their glucuronides. There are indications (Yue et al., 1997), that the analgesic effect is reduced in persons with low CYP2D6 activity (poor metabolizers). 

Pharmacokinetic properties Ethylmorphine (Aasmundstad et al., 1995) has a reasonable oral bioavailability. Like codeine, it is metabolized by O- and N-desalkylation, leading to nor-ethylmorphine, morphine, nor-morphine, and the respective glucuronides. 

Pharmacokinetic properties Levomethadone (Olsen et al., 1977) is readily absorbed from the intestinal tract and has high oral bioavailability. The compound is much more lipophilic than morphine and binds to plasma protein in the... 

The active substance is mechanically ejected from a blister through laser-drilled nozzles with a diameter of a few pm and integrated into the blisters by means of punch, to produce a mist consisting of drops measuring 1-6 pm. The blister is inserted into an electronically controlled dosing unit that measures the airstream and induces aerosolization in synchrony with inspiration. The bioavailability of morphine sulphate (total dose 8.8 mg) blistered in portions of 1.2 mg was 75% of that on intravenous administration (dose 4 mg), which is much higher than conventional aerosol formulations (Gonda et al., 1999 Otulana etal., 1999). 

Oxycodone is a semisynthetic opioid derived from thebaine and used for oral pain relief. It is commonly formulated as an immediate-re lease medication with acetaminophen or aspirin. A con-trolled-release oxycodone formulation is used for the treatment of moderate to severe pain it provides controlled drug delivery over 12 h. The oral bioavailability of this formulation is 60 to 87%.35 The results of clinical studies of patients with postoperative and cancer pain show that oxycodone has a potency 1.5 times that of morphine. 

FIGURE 8.3 Bioavailability of morphine after rectal administrations of Witepsol H-15 hollow-type suppositories containing morphine hydrochloride (MH) and CyDs in rabbits. Each value represents the mean SE of three rabbits. p < 0.05, compared with MH alone. 

Buccal delivery of opioid analgesics and antagonists can improve bioavailability relative to the oral route. Esterification of the 3-pheno-lic hydroxyl group in opioid analgesics such as nalbuphine, naloxone, naltrexone, oxymorphone, butorphanol, and levallorphan improved bioavailability and eliminated the bitter taste. The prodrug of morphine,... 

In Figure 2.4 the serum concentrations of three tablet forms of a drug are compared with its IV form. As you can see, tablets A and B have approximately the same bioavailability (AUC). Tablet C, on the other hand, has significantly less. Poor oral bioavailability can obviously influence a drug s ideal mode of delivery. It is because of poor oral bioavailability (approximately 25 percent) of heavily charged weak bases, such as the opiates (pKa values in the range of 8.0-9.0), that heroin and morphine abusers resort to injection of the drugs to maximize their effects. 

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