Bioavailability and Pharmacokinetics of a New Sustained-Release Potassium Chloride Tablet

The bioavailability of a new sustained-release potassium chloride (KC1) tablet, designed for once-a-day dosing, was compared to a KC1 elixir using urinary excretion data. The study utilized 25 male volunteers dosed in a crossover design in a dietary/activity-controlled environment. The regimens consisted of a total of 80 mEq of potassium in three equally divided doses of elixir every 6 hr and a single 80-mEq dose using four 20-mEq sustained-release (SR) tablets. The mean time to maximum rate of potassium urinary excretion was 2.2 hr for the first elixir dose and 5.5 hr after the SR tablet (P < 0.01), thereby supporting the prolonged-release properties of this formulation. After correction for baseline urinary potassium excretion, the mean total 24-hr urinary potassium excretion was 42.18 mEq for the elixir and 40.41 mEq for the SR tablet. The results indicate that the absorption pattern from the SR tablet is equal to three doses of KC1 elixir dosed 6 hr apart.     

西咪替丁对林可霉素生物利用度的影响

通过8名健康志愿者服药后的对照实验,用微生物法检测血药浓度,按一室模型配置求算药物动力学参数,探讨西咪替丁对林可霉素体内过程的影响。结果表明,西咪替丁不能改变林可霉素的吸收速率(Ka)和消除速率(Ke),但可通过增加其吸收程度或改变其分布容积,使林可霉素的血药浓度和生物利用度分别增加约19％和27％。     

Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Comparative kinetics of phenobarbital after administration of the acid and the propylhexedrine salt (barbexaclone)

Summary The kinetics of phenobarbital (PB) was compared after oral administration of equivalent doses of the drug as the acid or the propylhexedrine salt (barbexaclone) to 7 normal volunteers. The absorption and elimination parameters were very similar. It was concluded that propylhexedrine did not affect the serum kinetics of PB given as barbexaclone.     

Safety, tolerability and pharmacokinetic study of recombinant human parathyroid hormone in healthy male Chinese subjects

AIM： To determine the safety, tolerability and pharmacokinetic parameters of a new drug recombinant human parathyroid hormone [ rhPTH （1-84）] in healthy male Chinese subjects. METHODS： domly divided Thirty-six healthy male volunteers were rangroups received into 3 groups. The volunteers in these single subcutaneous injection of rhPTH （ 1-84） in a dosage of 1, 2 and 4 μg/kg respectively. Blood samples were obtained before and after administration within 24 hours. The rhPTH concentrations in sennn were determined by enzyme linked immunosorbent assay （ELISA）. The pharmacokinetic parameters determined with use of standard noncompartmental analysis were the maximum serum concentration （ Cmax ）, the time to attain that concentration （ tmax ）, and the area under the serum concentration-time curve up to 24 hours（ AUC0-24 ） and up to infinity （AUC0-∞）. Dose proportionality of pharmacokinetic parameters （AUC, Cmax of every volunteer of each dosage and A UC was computed from log transformed data） and was examined by mean of analysis of variance （ANOVA） using SPSS software package. In the study, subjects＇ symptoms, objective signs, and vital signs, including blood pressure, heart rate, respiratory rate and body temperature, were checked and 12-lead electrocardiography was recorded before and after drug administration within 24 hours. Routine laboratory tests, including hematology, blood biochemistry, serum electrolyte, and urinalysis, were performed before and after drug administration within at 24 hours.[第一段]     

环丙沙星的临床药物动力学研究

研究健康志愿者口眼和静脉滴注环丙沙星的药物动力学，并比较不同剂量、空腹与进餐、单剂与多剂给药的体内过程。单剂空腹口服环丙沙星５００ｍｇ后，Ｃｍａｘ为３．４８ｍｇ·Ｌ－１、为３．０１ｈ、ＡＵＣ为１４．１４ｈ．ｍｇ·Ｌ－１，静脉滴注环丙沙星２００ｍｇ后Ｃｍａｘ为６．５６ｍｇ·Ｌ－１、为３．７３ｈ，口服环丙沙星绝对生物利用度为６８．８９％。单剂空腹口服２５０、５００和１０００ｍｇ环丙沙星后，Ｃｍａｘ为１．８２～７．７２ｍｇ·Ｌ－１，为２．４７～３．１５ｎ，ＡＵＣ与剂量呈比例增加，进餐与空腹口服环丙沙星５００ｍｇ后的体内过程显示进食可使该药的吸收轻度减少。与单剂口服５００ｍｇ相比，５００ｍｇ日２次×７ｄ多剂给药后的Ｃｍａｘ和ＡＵＣ均较单剂者略增高，草剂口服２５０、５００、１０００和５００ｍｇ多剂量后２４ｈ尿排出率为给药量的４７％～５５％，静滴２００ｍｇ者为７１．０６％，基于上述药动学资料，拟订了环丙沙星对各种感染的治疗方案。     

枢复宁在肺癌患者体内的药物动力学和生物利用度

９名接受顺铂化疗的原发性肺癌患者单次口服和静脉注射枢复宁８ｍｇ后，用反相高效液相色谱法测定血浆药物浓度。经用ＰＫＢＰ－Ｎ１程序在计算机上拟合计算表明，枢复宁在人体内表现为二房室模型。口服后主要药动学参数：Ｔ１／２Ｋａ＝０．４１±０．３０ｈ，Ｔ１／２α＝０．９±０．４３ｈ，Ｔ１／２β＝３．３±１．２ｈ，Ｃｍａｘ＝２８．６±９．５ｎｇ／ｍｌ，Ｔｍａｘ＝１．７±０．９ｈ，ＡＵＣ＝１５８±７３ｎｇ·ｈ／ｍｌ，绝对生物利用度为５５％。     

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man

Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25  mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24  h post-dose.
Results Maximum plasma concentrations ( C _max ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25  mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C _max/AUC was increased by buffering. Time to C _max ( t _max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.     

地高辛临床药物动力学参数的预测及个体化给药方案

用Bayesian一点法拟合心衰病人的DG个体药物动力学参数及个体化给药方案,用minitab对软件DG群体药物动力学数据进行统计学分析.以CrCL为固定效应变量,建立系列回归模型,预测心衰病人的DG个体药物动力学参数、个体化给药方案及其对映的(?)ss.结果显示CrCL与DG群体药物动力学参数存在高度的相关(P<0.001),相关系数分别为:CL=0.805,Vd=0.985,T_(1/2)=-0.517,K=0.525,D_(1.0)=0.714.并建立定量回归模型,预测DG个体药物动力学参数,预测参数与实测参数没有统计学差异,其中以Vd预测精度最好,有95%的预测值在实测值的95%置信限以内.与实测值相关系数为0.974,估计标准误差小于3.3%;其次是CL,有2/3的预测值在实测值95%置信限以内,与实测值相关系数为0.797,估计标准误差小于20%;T_(1/2)和K预测结果稍差.CrCL预测的个体化给药方案80%符合最佳个体化给药方案,且两者所对应的(?)ss没有显著性差异.     

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5–10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.