ABSTRACT
While many studies have demonstrated the prevention of nausea and vomiting in patients receiving moderately or highly emetogenic anti-cancer agents, there are few reports of mildly emetogenic anti-cancer agents. In the present study, we performed a 2-year multi-center study to determine the types and efficacy of antiemetic therapy administered in a total of 77 cancer patients who received mildly emetogenic anti-cancer agents between September 2015 and August 2017. The effectiveness of antiemetic therapy was evaluated based on the frequency of nausea and vomiting and use of rescue medication. This information was reported by patients and collected every 24 hours for 120 hours after the administration of anti-cancer agents with a mild emetogenic risk. The combination of 5-HT3 receptor antagonist(1 or 3 mg granisetron, 0.75 mg palonosetron) and 6.6 mg dexamethasone was the most common antiemetic therapy used in our patient population. There was no significant difference in the effectiveness of all 5-HT3 receptor antagonists that were evaluated. Gemcitabine and nab-paclitaxel were the most commonly used with a total of 64 patients receiving a combination of these mildly emetogenic agents. Poor performance status was associated with failure to achieve total control(TC)of nausea and vomiting(p=0.0304), while habitual alcohol consumption was associated with TC of nausea and vomiting(p=0.0331).
Subject(s)
Antiemetics/therapeutic use , Nausea/prevention & control , Vomiting/prevention & control , Antineoplastic Agents , Dexamethasone , Humans , Quinuclidines , Surveys and QuestionnairesABSTRACT
To optimize polymer-conjugated drugs as a polymeric drug delivery system, it is essential to design polymeric carriers with tissue-specific targeting capacity. Previously, we showed that polyvinylpyrrolidone (PVP) was the most suitable polymeric carrier for prolonging the blood-residency of drugs, and was one of the best parent polymers to design the polymeric carriers with targeting capacity. In this study, we synthesized some hydrophobic PVP derivatives, poly(vinylpyrrolidone-co-styrene) [poly(VP-co-S)] and poly(vinylpyrrolidone-co-vinyl laurate) [poly(VP-co-VL)], and assessed their biopharmaceutical properties after intravenous administration in mice. The elimination of hydrophobic PVP derivatives from blood was the same as PVP, and the plasma half-lives of poly(VP-co-S) were almost similar to that of poly(VP-co-VL). Poly(VP-co-VL) efficiently accumulated in the spleen, whereas poly(VP-co-S) effectively accumulated in the liver. The level of poly(VP-co-VL) in the spleen was about 20 times higher than PVP and poly(VP-co-S). These hydrophobic PVP derivatives did not show any cytotoxicity against endothelial cells in vitro. Thus, poly(VP-co-VL) may be a useful polymeric carrier for drug delivery to the spleen. This study will provide useful information to design optimal polymeric carriers with targeting capacity to the spleen and liver.
Subject(s)
Biocompatible Materials/pharmacokinetics , Povidone/pharmacokinetics , Spleen/metabolism , Animals , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Delivery Systems , Fluorescence , Hydrophobic and Hydrophilic Interactions , Male , Materials Testing , Mice , Molecular Conformation , Povidone/chemical synthesis , Povidone/chemistry , Tissue DistributionABSTRACT
Poly(vinylpyrrolidone-co-dimethyl maleic acid) (PVD) was found to have high renal-targeting capability and safety as a drug carrier. To optimize the renal drug delivery system using PVD, the relationship between the molecular weight of PVD and its renal accumulation were evaluated in mice by their intravenous injection. It was found that the molecular size of 6-8 kDa was associated with the highest renal accumulation. The specific bioactivity of PVD-conjugated superoxide dismutase (SOD) relative to that of unmodified SOD gradually decreased with an increase in the degree of modification to SOD with PVD6K. The conjugated SOD (L-PVD-SOD) with the molecular size of 73 kDa, which had comparable specific bioactivity with native SOD, showed longer plasma half-life than native SOD. About sixfold more L-PVD-SOD was distributed to the kidneys than native SOD 3 h after intravenous injection, whereas extensive PVD modification did not enhance the renal accumulation of SOD. This L-PVD-SOD effectively accelerated recovery from mercuric chloride-induced acute renal failure in vivo. These results suggest that L-PVD-SOD may be the optimal derivative as a potential therapeutic agent to various renal diseases.
Subject(s)
Drug Delivery Systems , Kidney/metabolism , Pyrrolidines/chemistry , Vinyl Compounds/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/drug therapy , Animals , Drug Carriers , Iodine Radioisotopes , Male , Mercuric Chloride/administration & dosage , Mercuric Chloride/pharmacokinetics , Mercuric Chloride/toxicity , Mice , Mice, Inbred BALB C , Molecular Weight , Superoxide Dismutase/administration & dosage , Superoxide Dismutase/pharmacokinetics , Superoxide Dismutase/therapeutic use , Tissue DistributionABSTRACT
We have synthesized a polymeric drug carrier, polyvinylpyrrolidone-co-dimethyl maleic anhydride [poly(VP-co-DMMAn)], for use in renal drug delivery. About 80% of the 10-kDa poly(VP-co-DMMAn) selectively accumulated in the kidneys 24 h after intravenous administration to mice. Although this accumulated poly(VP-co-DMMAn) was gradually excreted in the urine, about 40% remained in the kidneys 96 h after treatment. Poly(VP-co-DMMAn) was taken up by the renal proximal tubular epithelial cells and no cytotoxicity was noted. Higher doses did not produce toxicity in the kidneys or other tissues. In contrast, polyvinylpyrrolidone of the same molecular weight did not show any tissue-specific distribution. Poly(VP-co-DMMAn)-modified superoxide dismutase accumulated in the kidneys after intravenous administration and accelerated recovery from acute renal failure in a mouse model. In contrast, polyvinylpyrrolidone-modified superoxide dismutase and native superoxide dismutase were not as effective. Thus, poly(VP-co-DMMAn) is a useful candidate as a targeting carrier for renal drug delivery systems.