Compartmental analysis of ranitidine doubled peak plasma profile after oral administration to healthy volunteers

Abstract

The aim of this study was to describe the double peak plasma pharmacokinetic profile of ranitidine after oral administration to healthy volunteers using non-compartmental and compartmental analysis. A single 300 mg dose of ranitidine was given to ten healthy volunteers (5 male and 5 female). Blood samples were drawn at different times and analyzed by HPLC. Plasma profiles were evaluated by non-compartmental and compartmental approaches. The non-compartmental parameters determined were k (0.0054 ± 0.0010 min -1 ), t 1/2 (2.2 ± 0.4 h), Vd ss /F (265.3 ± 70.6 L), Cl/F (84.8 ± 24.3 L/h) and AUC (225916 ± 54099 ng*min/mL). The compartmental analysis was carried out using a two compartments body model, with first order absorption from two different sites. The parameters determined were k 21 (0.0149 ± 0.0133 min -1 ), k a1 (0.0117 ± 0.0073 min -1 ), k a2 (0.1496 ± 0.1699 min -1 ), Vc (128 ± 75.2 L), a (0.0299 ± 0.0319 min -1 ), b (0.0074 ± 0.0014 min -1 ) and time for the beginning of the absorption from the second site (126.7 ± 58.1 min). The model used in the compartmental analysis was adequate to describe the double peak of ranitidine plasma profile and to determine the pharmacokinetic parameters.

Therapeutic drug monitoring and pharmacokinetic compartmental analysis of sulpiride double‐peak absorption profile after oral administration to human volunteers

“…Here a double-peak phenomenon in the serum concentration-time profiles of sulpiride via oral administration was reported. Similar double-and multiple-peak phenomena have been described for many structurally diverse compounds such as veralipride [21], danazol [22], acebutolol [23], alprazolam [24] and ranitidine [25,26] after oral doses, but such a phenomenon has not been reported for sulpiride.…”

“…Both C max and t max observed in this study showed an inter-subject variation to some extent, which may be explained by using the discontinuous absorption model suggested by Suttle et al [34], which divided the gastrointestinal tract in this model into compartments connected according to a catenary system with drug absorption occurring only in the first and last compartments [26,34]. Based on the simulations coined by these authors using the discontinuous absorption model, the intensity and variability of C max and t max observed could be related to the following factors: the dose administered, the drug transfer rate from the stomach to the first site of absorption, the number of gut compartments, the distance between the two absorption sites, the drug transfer rate among the compartments, and the absorption rate at each site of absorption [26].…”

“…This is because sulpiride is considered to be a suitable probe drug for intestinal P-gp, the variability of its oral PKs should reflect the variability of the P-gp function that is believed to be very important for the absorption window and elimination of sulpiride. The doublepeak phenomenon due to two different sites of drug absorption in the gut has been reported previously in the case of penicillamine [53], veralipride [21], piretanide [54], pafenolol [55], cimetidine [56] and ranitidine [26].…”

“…Double peaks in the plasma concentration-time profile following oral administration have been reported for several compounds [21][22][23][24][25][26]; however, this is the first reported study of double peaks in sulpiride. Whereas, this phenomenon was observed for another benzamide neuroleptic drug, veralipride, by Plusquellec and his coworkers in 1987 [21].…”

“…The schematic representation of the model is shown in Figure 1. The equation that describes the drug concentration in the central compartment of this model is shown below [26,33,34]:…”