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Researchers find that new use for old drug equals more milk

Holly Drankhan for Progressive Dairyman Published on 24 February 2016

A single bolus – that is all a cow may require to increase her milk yield and longevity, according to a study recently published in the Journal of Dairy Science.

Researchers from Kansas State University and Iowa State University investigated the effects of treating postpartum cows with two non-steroidal anti-inflammatory drugs (NSAIDs): meloxicam and sodium salicylate.

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Their interest spawned largely from a 2013 study, which found that cows in their third or greater lactation produced 21 percent more milk in a 305-day period if sodium salicylate – a relative of aspirin – was incorporated into their drinking water for a week after calving.

This method of administration is not practical for most dairy farmers, says Abigail Carpenter, the study’s lead author. Therefore, the new study set out to demonstrate the efficacy of methods that could more easily be incorporated into normal farm routines.

To do so, the team partnered with Prairieland Dairy in Firth, Nebraska. They divided 153 dairy cows in their second or greater lactation evenly into three treatment groups.

One group received a placebo bolus on the first day followed by three daily drenches of sodium salicylate, a highly water-soluble compound. Members of the second treatment group each received a 675-mg bolus of meloxicam and three drenches of water.

Cows in the control group were administered a placebo bolus on the first day and drenches of water for three subsequent days.

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Across all groups, drugs were first administered 12 to 36 hours postpartum. If given too soon following parturition, NSAIDs could lead to retained placentas and fetal membranes as well as metritis, Carpenter says. NSAIDs administered at dry-off could also interfere with normal inflammation associated with mammary gland involution, she adds.

“It was a small window of time that we were looking at when we weren’t necessarily going to have any of those negative effects of medication but still capture some of the higher-risk time,” Carpenter says.

The team compared blood samples pre-treatment with those immediately following and seven days after treatment. They also measured body condition score, milk production, reproductive status and retention in the herd for a year post-treatment.

Both meloxicam and sodium salicylate increased daily milk yield compared to the control group after seven weeks. A 7 to 9 percent increase in 305-day whole-lactation milk yield was also noted for both NSAID treatments, as was an increase in protein yield.

Several previous studies with NSAIDs did not document a comparable increase in milk yield. Factors that could account for this discrepancy include differences in the mode of action among NSAIDs, methods of administration, dosages and the amount of time after calving when drugs were administered, according to the study.

In the current study, an increase in milk yield among the NSAID-treated groups first became statistically significant at seven weeks into lactation. It is possible that some previous studies did not monitor milk production long enough to observe these differences, Carpenter says.

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In addition to increasing milk yield, the study found that cows that received a meloxicam bolus stayed in the milking herd longer than cows in the control group. After a year, only 13 meloxicam-treated cows left compared to 21 control cows.

So what are the drawbacks?

This use for both meloxicam and sodium salicylate is extra-label, and drugs cannot be used off-label for production purposes outside of a research setting, says Dr. Paul Biagiotti, a bovine veterinarian in Jerome, Idaho.

Injectable meloxicam is approved in Canada for treatment of mastitis, which could reduce early lactation inflammation in treated cows, says Barry Bradford, associate professor at KSU and a corresponding author for the study. Kansas State University has filed a patent on the use of NSAIDs to increase whole-lactation milk yield and herd retention, he says.

“At this point, interested pharmaceutical companies could license the provisional patent and conduct the studies required to gain FDA approval for such claims, but I’m not sure if or when any will decide to do so,” Bradford says, adding that investigational animal drug applications with the FDA cost more than $100,000.

Gary Neubauer, senior manager of dairy technical services for Zoetis, says that with regard to the dairy industry, Zoetis is working to gain approval for products that are on-label.

Another drawback is that both treatments required the discarding of milk to avoid drug residues. While there are no official U.S. guidelines for either drug, the team discarded milk for 10 days following treatment to avoid uncertainty.

Data suggest that a 24-hour withdrawal period would be adequate for sodium salicylate, while meloxicam would require four to five days, according to the study.

“The increased 305-day milk production that we observed can compensate for loss of milk revenue during the withdrawal period, but the inconvenience of segregating milk from these cows could limit adoption of postpartum NSAID treatment on dairies,” wrote the authors.

Drenches always come with the risk of aspiration pneumonia, Biagiotti says. Producers also want to minimize the amount of time fresh cows are restrained, he adds. Cost and labor are other considerations should the drugs be approved for this use.

Moving forward, researchers plan to investigate the mechanisms responsible for the large and delayed biological effects, as well as identify nutritional agents that work in a similar way, Bradford says. They also look to replicate the results with other NSAIDs.

“Dairy science is a mature science, and the dairy industry is very sophisticated,” he says. “That being the case, it is very unusual to uncover a simple intervention that has production effects in the range of a 10 percent response, especially across the entire lactation.

Therefore, uncovering biology this powerful is extremely exciting to me; even if our current approach does not end up being directly applied (for regulatory reasons or others), I am very optimistic that we will eventually be able to put this biology to use to make the industry more sustainable than it is today.”

Carpenter is also optimistic about the results.

“A lot of my research has dealt with nitty-gritty physiological mechanisms, and sometimes you kind of get so turned into the minutia of what is going on that you forget the big picture,” she says.

“It is really exciting for me to be able to see that what we are doing can essentially have an impact on what dairy farmers in the U.S. are going to be doing five, 10 or maybe 20 years from now.”  PD

Holly Drankhan is a student at Michigan State University College of Veterinary Medicine.

References omitted due to space but are available upon request. Click here to email an editor. 

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