Paracetamol bioavailability

Magnesium silicate may decrease the oral bioavailability of drugs such as mebeverine hydrochloride, sucralfate, and tetracycline, via chelation or binding, when they are taken together. The dissolution rate of folic acid, erythromycin stearate, paracetamol, " and chloroquine phosphate, " may be retarded by adsorption onto magnesium silicate. Antimicrobial preservatives, such as parabens, may be inactivated by the addition of magnesium silicate. ... 

Vila-Jato JL, Blanco J, Alonso MJ. The effect of the molecular weight of polyethylene glycol on the bioavailability of paracetamol-polyethylene glycol solid dispersions. / Pharm Pharmacol 1986 38 126-128. 

In a smdy of the various physical properties of suppositories, the most important parameter for the bioavailability of paracetamol was found to be their rheological properties at 37°C. The relationship between the excretion of paracetamol (APAP N-acetyl-p-aminophe-nol) and the rheology of the excipient dmg suspension is shown in Fig. 9.55. The greater the limiting shear stress, r, of the system, the lower the bioavailability of the dmg. 

The principal sites for sulfation reactions are the liver and kidneys, although an important site, especially after oral administration of drugs, is the small intestine. Sulfation in the gut can seriously affect the bioavailability of some drugs such as paracetamol (see Figure 5.3) and is the main reason why adrenaline (epinephrine) is not effective when given orally... 

The poor compression of paracetamol was addressed through the preparation of a new orthorhombic form [55]. Owing to its well-known poor compressional properties, commercially available paracetamol materials for direct compression are compounds of paracetamol with gelatin, polyvinylpyrrolidone, starch, or starch derivatives. Since a chemically pure paracetamol that could be used for direct compression would constitute a better compendial article, a new polymorph was produced. The new form was recrystallized from dioxane, and its crystals were found to consist of sliding planes that led to good compressibility. However, the orthorhombic form is metastable with respect to the monoclinic form phase conversion was observed if the raw material contained greater than 20% of the monoclinic phase. However, the dissolution rates for the two forms were found to be similar, and therefore any questions as to the relative bioavailability of the two forms would probably be meaningless. 

Rectal absorption of drugs may be slow and unpredictable in the neonatal period, although it is a useful route when other methods are not available. The relative bioavailability may also be influenced by the rate of hepatic metabolism. The absorption of drugs from the rectum is also influenced by the rate of expulsion. Infants have a greater number of rectal contractions than adults (Di Lorenzo et al, 1995), which may enhance the expulsion of the dose and reduce absorption of drugs such as paracetamol (van Lingen et ah, 1999). 

Diflunisal. Diflunisal significantly raised serum paraeetamol levels by 50% but the total bioavailability was unehanged in healthy subjects. Diflunisal levels were not affected. This interaetion has not been shown to be clinically important. Nevertheless, the manufaeturer of diflunisal ree-ommends that the combination should be used with eaution, beeause ofthe association of high levels of paracetamol with hepatotoxieity. ... 

Hemmii JD, Bird HA, Pidaq) ME, Saunders A, Lowe JR, Dboan JS. Bioavailability of aspirin in the presence of dexbD Dpo hene/paracetamol combinatioiL Phanna terapeutica (1981)2,543-6. 

Tukker JJ, Sitsen JMA, Gusdorf CF. Bioavailability of paracetamol after oral administration to healthy volunteera. Influence of caffeine on rate and extent of absorption. Pharm Weeldyl (Sci) (1986) 8,239-43. 

Food slows the rate of absorption of paracetamol, but the overall bioavailability is not usually affected. However, in some individuals food may delay and reduce peak paracetamol-plasma levels. A high fat meal may slightly reduce the extent of paracetamol absorption and certain foods, such as cabbage and brussels sprouts, may affect the metabolism of paracetamol, but this is unlikely to be clinically significant. 

Propranolol may slightly increase the bioavailability of paracetamol, but this is unlikely to be clinically significant. 

The bioavailability of paracetamol 1 g (using salivaiy paracetamol levels over 4 hours as a measure of paracetamol absorption) was found to be unchanged in 6 healthy subjects given sucralfate... 

Itoh H, Nagano T, Takeyama M. Cisapride raises the bioavailability of paracetamol by inhibiting its glucuronidation in man. JPharm Pharmacol (2001) 53, 1041-45. 

To improve the absorption and bioavailability, paracetamol in suppositories is processed as particles < 45 pm. In powders because of the greater density and better flow properties paracetamol (500-90) is used and for solutions either product can be used. 

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