Rectal Bioavailability of Bacampicillin Hydrochloride in Man as Determined by Reversed-Phase Liquid Chromatography

Abstract

The relative bioavailability of bacampicillin hydrochloride, a pro-drug of ampicillin, was compared after rectal and oral administration. Bacampicillin was administered rectally as a microenema. The oral formulation was an aqueous microcapsule suspension. They were given as single doses of 400 mg to 12 healthy volunteers after overnight fasting using a randomized cross-over design. Ampicillin and bacampicillin were determined in plasma and blood, respectively, using HPLC. Bacampicillin was rapidly absorbed from the rectum but to a much smaller degree compared to the oral dose. The median t-max was 0.5 and 0.75 h after the rectal and oral doses, respectively. The mean (SD) C_p-max was 1.2 (0.33) mg/l after rectal and 4.8 (0.98) mg/l after oral administration, respectively. Blood concentrations of bacampicillin were extremely low or undetectable with no indication of differences between the two modes of administration. The 95% confidence limits for the relative bioavailability of the microenema were 22.4–39.2 and 22.5–40.4% based on area under the plasma concentration time curve and urinary recovery, respectively. The rectal dose was followed by distress, diarrhea or pain, in 7 subjects. There were no adverse reactions after the oral dose. Bacampicillin was unaffected by β-lactamases produced by intestinal bacteria.

Renal excretion of intravenously infused amoxycillin and ampicillin.

“…In conformity with the episode in this study, subject No. 3 experienced a similar taste sensation after a rectal dose of bacampicillin, a prodrug of ampicillin (Sjovall et al, 1984). This effect therefore seems to be consistent in this subject but it has not been recorded after intravenous or rectal penicillin in any other subject in our studies.…”

Rectal ropivacaine is absorbed proportionally to the dose, with low intraindividual variability

“…The rectal mucosa and the anal canal were inspected by rigid procotosigmoidoscopy between 1 and 2 days before and at 22-26 h after each dose, by the same physician who was blinded to treatment. The rectal mucosa was inspected for the degree of hyperaemia, redness, oedema, ulceration, tendency to bleed, fragility and vascular distribution, all of which were graded as normal, slightly changed or substantially changed, according to methods described previously [17]. Redness, epithelium defects, ulceration, the presence of fissures and mucosal prolapse were assessed in the anal canal using the same grading system.…”

Enemalar Ve Enema Formülasyonlarinda Yeni̇ Geli̇şmeler Enemas and New Developments in Enema Formulations : Enemas and New Developments in Enema Formulations

“…Ancak oral uygulama ile kıyaslandığında düşük biyoyararlanım elde edilmesi, küçük absorpsiyon yüzeyinden, pH 7-8 civarındaki rektal pH'da etken maddenin çözünürlüğünün az oluşundan ve rektum tamponlama kapasitesinin çok az olmasından kaynaklandığı kanısına varılmıştır. Ayrıca viskozite artırarak rektal mukoza ile temasın artırılmasına çalışılırken bakampisilin'in metil selüloza bağlanmış olması ihtimali de ileri sürülmüş, hatta bu bağlanmanın azalabilmesi için ultrafiltrasyon yapılmıştır(39).Akut astım vakalarında sempatomimetik ilaçlara ilaveten teofilin'in IV uygulamaları da yapılmaktadır. Teofilin, diprofilin, proksifilin kombinasyonu ile hazırlanan retansiyon enemasının teofılin-etilendiamin IV formülasyonu ile karşılaştırmasının yapıldığı bir çalışmada enema ile IV uygulamaya göre daha uzun bir sürede maksimum seviyeye ulaşmasına rağmen, yüksek serum teofılin seviyesi sağlayabildiği ve daha uzun süreli olarak etkin konsantrasyonda kalabildiği tespit edilmiştir (40).…”