Supramolecular aggregates formed by sulfadiazine and sulfisomidine inclusion complexes with α- and ß-cyclodextrins.

Sulfadiazine (SDA) and sulfisomidine (SFM) inclusion complexes with two cyclodextrins (α-CD and ß-CD) are studied in aqueous as well as in solid state. The inclusion complexes are characterized by UV-visible, fluorescence, time correlated single photon counting, FTIR, DSC, PXRD and (1)H NMR techniques. The self assembled SDA/CD and SFM/CD inclusion complexes form different types of nano and microstructures. The self assembled nanoparticle morphologies are studied using SEM and TEM techniques. SDA/α-CD complex is formed hierarchal morphology, SDA/ß-CD and SFM/ß-CD complexes form the nanosheet self assembly. However, SFM/α-CD complex forms nanoporous sheet self assembly. van der Waals, hydrophobic and hydrogen bonding interaction play a vital role in the self assembling process.

Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the dissociation of the drug.

We aimed to clarify the relationship between drug dissociation (sulphisomidine) and its direct transport from the nasal cavity to the cerebrospinal fluid (CSF). Rat nasal cavities were perfused in a single pass system with buffers (pH 5.5, 6.5, 7.4, 8.7 and 9.4). Plasma and CSF were collected and the concentration of sulphisomidine was measured. Nasal clearance increased with the increase in the un-ionized fraction of the drug. The ratio of the drug concentration in CSF to that in the nasal perfusion fluid (the index of the degree of the drug transport from the nasal cavity to CSF), was changed in accordance with the un-ionized fraction of drug. These results show that both the nasal absorption and the drug transport conform to the pH partition theory.

Pharmacokinetics of three sulphonamides in ruminant and preruminant kids.

The pharmacokinetic properties of three sulphonamides were determined in ruminant and preruminant kids after oral and intravenous administration. First, sulphisomidine (SIM, 50 mg kg-1) and sulphadoxine (SDX, 30 mg kg-1) were given to seven kids, 10 to 12 weeks old, while on a milk replacer diet and again at 15 to 18 weeks when fed roughage. Secondly, SIM (100 mg kg-1) and sulphadimidine (SDD, 100 mg kg-1) were given at six to nine, 12 to 15 and 18 to 21 weeks old to eight kids, of which four were fed milk replacer and four were with their mothers (with access to roughage) until 15 weeks, after which all were fed roughage only. SDX and SDD exhibited non-linear (or capacity limited) absorption after oral dosage, suggesting possible active absorption mechanisms, and both drugs also showed non-linear elimination. Intravenous curves for SDD and SIM indicated that recycling occurred. With SDX, ruminant kids showed poorer systemic availability after oral dosage, shorter t1/2(el) and higher B than did preruminants. For SDD, ruminant kids had lower Vd and higher B than preruminants. SIM's t1/2(el) tended to shorten and beta to increase in both groups throughout the experiment. Not all differences between ruminants and preruminants in sulphonamide pharmacokinetics could be explained by the accumulation of acidic forestomach contents and the change of urine pH from acid to alkaline in the maturing ruminant. Other potential contributing factors require investigation, including possible alterations in hepatic drug metabolism. Of the three drugs tested, SDX might be the most satisfactory for therapeutic use in preruminant animals, because it has good bioavailability after oral administration and long t1/2(el).

Therapeutic equivalence of sulfaisodimidine 2 g twice daily and 1 g four times daily in lower urinary tract infections.

The serum concentrations and clinical effects of sulfaisodimidine given during 12 days were examined in two groups of patients with uncomplicated lower urinary tract infection. Group I (n=12) received the drug in a conventional dosage, 1 g four times daily, and group II (n=14) in a dose of 2 g twice daily. The serum concentrations of sulfonamide at steady state (day 7) and one day after cessation of therapy (day 13) did not differ significantly between the groups. With the exception of one patient in group I, both subjective and objective symptoms vanished during treatment and remained absent for at least 4 weeks thereafter. Two patients in each group developed signs of sulfonamide allergy. Thus, the two regimens seemed to be equally efficient, and the risk of therapy failure due to low blood concentrations of sulfaisodimidine should not be greater when the drug is given in a dosage of 2 g twice daily than when it is administered in the conventional way. Hence, the latter, simpler regimen can be recommended.

[Enteral absorption of sulfasomidine depending on age (author's transl)]. / Enterale Absorption von Sulfasomidin in Abhängigkeit vom Lebensalter.

After intravenous and oral application of 25 mg 6-(sulfanilamido)-2,4-dimethyl-pyrimidine (sulfasomidin)/kg body-weight to 29 newborns, 8 infants and 9 older children the completeness and rate of absorption were determined. Sulfasomidine was completely absorbed in newborns (mean value 95.7%) as well as in older children (mean value 94.4%). Concerning the rate of absorption there were age-dependent differences. Using the Bateman function for the kinetic model of intestinal absorption the rate constant of invasion k1 was significantly lower in the first week of life compared to that in older children. In agreement with these data the time tmax of the maximum serum concentration was significantly prolonged in newborns compared to that of older children.