Hepatic first-pass effect and controlled drug delivery following rectal administration

Diclofenac pharmacokinetic meta‐analysis and dose recommendations for surgical pain in children aged 1–12 years

“…A major finding of this study was that rectal bioavailability of diclofenac is almost twice that of oral diclofenac. This is probably because of the high pH in the rectum allowing for efficient drug dissolution (diclofenac pKa is around 4.2, so it is insoluble in acidic conditions) and that the middle and inferior rectal veins bypass the liver (25), meaning diclofenac undergoes less‐extensive first‐pass metabolism by this route. A relatively common adverse effect of diclofenac suppositories is rectal irritation, which occurs in 0.3% (95% CI 0.009, 1.9) of pediatric subjects (26), so the finding that efficacy of 0.5 mg·kg −1 is likely to be similar to 50 mg in adults means that we recommend using the lower end of the current British National Formulary (27) dose range of 0.5–1 mg·kg −1 .…”

The effects of morphine and methylnaltrexone on gastrointestinal pain in healthy male participants

“…Thus, the opioid receptors may not be involved in nociception. (ii) It could be speculated that morphine does not bind to the peripheral opioid receptors in the gut but bypasses the peripheral nervous system and directly enters the systemic circulation . (iii) Although several clinical studies have demonstrated peripheral mediated reduction in pain after local application of opioids to other tissues and not only the intestinal tract, it has been speculated that analgesic effect is less pronounced in non‐inflamed tissue .…”

Pathways of paracetamol absorption from layered excipient suppositories: artificial intelligence approach

“…In the case of paracetamol rectal availability the use of partially fuzzyfied model allowed systemic combination of all described mechanisms found in the literature (6)(7)(8)(9)(10) and measured data. In spite of non-identifiability,the model showed that patterns that explained differences in bioavailabilities of the two formulations of suppositories could be found.…”

“…There is also a large number of articles, each dealing with only one or with a few of the mechanisms that are evaluated separately (6)(7)(8)(9)(10). However, there is little information available on how the mechanisms interact in the organism and thus govern the pharmacokinetics of the drug, which means that systemic view in the expert knowledge is missing.…”