BIOLOGICAL AVAILABILITY AND IN VITRO DISSOLUTION OF OXYTETRACYCLINE DIHYDRATE TABLETS

Abstract

The concentration of oxytetracycline in plasma was studied by microbiological assay after oral administration of four different preparations of oxytetracycline dihydrate tablets. There were statistically significant differences in biological availability between the four preparations, as assessed by the peak plasma level, the area under the plasma concentration‐time curve, or the cumulative fraction of the dose excreted in urine at 405 minutes. In contrast, differences between the subjects were not statistically significant. The differences in biological availability were not predictably related to the in vitro dissolution of the tablets.

Bioavailability and dissolution of different formulations of oxytetracycline preparations.

“…The correlation between the mean maximum plasma levels (Table 3) and the mean t5o values (Table 2) was statistically significant (r = -0.900; 0.02 > P > 0.01). As shown in other studies (Scales & Assinder, 1973;Barber et al, 1974), there was a marked variation in individual plasma levels with all five preparations, as indicated by the large standard errors (Table 3). In consequence, statistically significant differences (P < 0.05) were not obtained between the mean plasma levels of different preparations, except with tablets B and D. As shown in Table 3, differences between these two preparations were statistically significant at 90, 120, 180, 270, 360 and 405 minutes.…”

“…Differences in the biological availability of commercial preparations of tetracyclines have been reported by authors in the United States (Brice & Hammer, 1969;Macdonald, Pisano, Burger, Dornbush & Pelcak, 1969), Holland (Altmann, Beeuwkes, Brombacher, Buytendijk, Gigen & Maesen, 1968), Scandinavia (Bergen, Oydvin & Lunde, 1972;Tuomisto & Mannisto, 1973) and Britain (Barnett, Smith, Greenwood & Hetherington, 1974;Barber et al, 1974). In most of these studies bioavailability was assessed by the area under the plasma concentration-time curve or the urinary elimination of the antibiotic.…”

“…In most of these studies bioavailability was assessed by the area under the plasma concentration-time curve or the urinary elimination of the antibiotic. In one instance, there was a rank correlation between tetracycline excretion in urine and dissolution in vitro in simulated gastric juice (Macdonald et al, 1969), although the relationship between bioavailability and acid dissolution was generally less well defined (Brice & Hammer, 1969;Barnett et al, 1974;Barber et al, 1974). These studies have generally been concerned with standard products of several manufacturers, and it is usually accepted that variations in both bioavailability and dissolution are related to differences in the formulation of the antibiotic.…”

“…The biological availability of these different preparations is partly dependent on their rapid solution in gastric secretions. In in vivo conditions, the solubility of oxytetracycline hydrochloride may be considerably greater than the dihydrate (Barber, Calvey, Muir & Hart, 1974), although there are no published studies on the relative bioavailability of these two compounds. We have therefore compared the biological availability of three preparations of oxytetracycline dihydrate (including both film-coated and sugar-coated tablets), as well as two formulations of the hydrochloride.…”

“…We have therefore compared the biological availability of three preparations of oxytetracycline dihydrate (including both film-coated and sugar-coated tablets), as well as two formulations of the hydrochloride. None of these preparations was studied in our previous paper (Barber et al, 1974); all of them were made by one manufacturer.…”