Tolerability of up to 200 days of prophylaxis with valganciclovir oral solution and/or film-coated tablets in pediatric kidney transplant recipients at risk of cytomegalovirus disease.

This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101-228 vs days 1-100. Twenty-seven patients (48.2%) had treatment-related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment-related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy-proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.

AC biosusceptometry technique to evaluate the gastrointestinal transit of pellets under influence of prandial state.

Multiparticulate dosage forms have been proposed when distal regions of gastrointestinal tract are desirable as target of drugs. It is known that physiological parameters might interfere with the processes related to the drug delivery and absorption and therefore, it is essential to evaluate the behavior of such delivery systems in vivo. The aim of this study was to propose the AC Biosusceptometry technique as a noninvasive and radiation free device to evaluate the gastrointestinal transit of a magnetic multiparticulate dosage form in healthy volunteers under fasting and fed conditions. Magnetic pellets were prepared by the powder layering method of ferrite on nonpareils sugar beads and coated by using Eudragit. Our data showed that the AC Biosusceptometry technique was able to monitoring the gastrointestinal transit of pellets presenting similar profiles as demonstrated by standard techniques. Food intake has markedly influenced the gastric emptying as well as the colon arrival and the small intestine transit of magnetic pellets.

Gastrointestinal transit and disintegration of enteric coated magnetic tablets assessed by ac biosusceptometry.

The oral administration is a common route in the drug therapy and the solid pharmaceutical forms are widely used. Although much about the performance of these formulations can be learned from in vitro studies using conventional methods, evaluation in vivo is essential in product development. The knowledge of the gastrointestinal transit and how the physiological variables can interfere with the disintegration and drug absorption is a prerequisite for development of dosage forms. The aim of this work was to employing the ac biosusceptometry (ACB) to monitoring magnetic tablets in the human gastrointestinal tract and to obtain the magnetic images of the disintegration process in the colonic region. The ac biosusceptometry showed accuracy in the quantification of the gastric residence time, the intestinal transit time and the disintegration time (DT) of the magnetic formulations in the human gastrointestinal tract. Moreover, ac biosusceptometry is a non-invasive technique, radiation-free and harmless to the volunteers, as well as an important research tool in the pharmaceutical, pharmacological and physiological investigations.