Published online Oct 21, 2017. doi: 10.3748/wjg.v23.i39.7098
Peer-review started: July 24, 2017
First decision: August 15, 2017
Revised: August 27, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: October 21, 2017
Oral administration with Da-Cheng-Qi decoction (DCQD) is the conventional therapy at the early phase of acute pancreatitis (AP) patients in China. But oral dosing with DCQD is contrary to the idea of pancreatic rest at the early stage of AP, which may inhibit the absorption of the components of DCQD, influence its pharmacokinetics or pharmacodynamics and even worsen the disease severity.
The necrosis of pancreatic acinar cells would worsen the disease and the induction of apoptosis would relieve the disease severity. In clinical practice, oral dosing or coloclysis of DCQD are performed immediately when patients with AP are admitted to hospital. Whether these approaches could increase secretion of gastrointestinal tract remain unclear. What’s more, little research on the optimal administration time of Chinese herbs has been reported, and there are no definite opinions on this topic in the Chinese guidelines. Thus, based on effect of DCQD regulating the apoptosis/necrosis switch of pancreatic acinar cells to ameliorate the pancreatic inflammation and pathological damage, the study aimed to screen the optional oral dosing time of DCQD in rats with AP according to the pharmacokinetics of the absorbed components and the pharmacodynamics of DCQD targeting of pancreas.
This objective was to screen the optional oral dosing time of DCQD in rats with AP based on the pharmacokinetic and pharmacodynamic parameters. We hoped to find an optimal dosing time of DCQD without increasing the severity of AP.
This animal experiment was divided into pharmacokinetic and pharmacodynamic parts. AP models were induced by 3% sodium taurocholate. Rats were dosed at three different times. Plasma samples were collected from the tails at nine different times. The main components’ concentrations of plasma and pancreatic tissues were detected by high-performance liquid chromatography tandem mass spectroscopy, confirmed as a specific, sensitive, accurate and reproducible method. The pharmacokinetic parameters [the maximum plasma concentration (Cmax), the time to reach maximum concentration (Tmax), the mean residence time (MRT0→t), the elimination half-life (T1/2) and the area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration (AUC0→t)] were processed by pharmacokinetic statistical software DAS2.0.1 programmed by the Chinese Pharmacological Society. The IL-10, IL-6 and amylase concentrations in serum and pathological scores of pancreatic tissues were calculated.
According to the present study, AP reduced the concentrations of the major components of DCQD to the target pancreas, and the oral administration time also played an important role. AP delayed the Tmax and reduced the Cmax of the components of DCQD in the circulation of rats. The AUC0→t was larger when that time was approximately 12 h after the onset of AP. DCQD increased the IL-10 levels and lowered the IL-6 levels, and the later administration of the DCQD dose corresponded to higher IL-10 levels. Therefore, administering the DCQD dose too early may not be appropriate for AP. However, our results need further clinical studies to be confirmed.
Late-time dosing may result in higher concentrations of the major components of DCQD with better pharmacokinetics and pharmacodynamics of anti-inflammation than seen with early-time dosing, thereby showing the late time to be the optimal dosing time of DCQD for AP.