Pedro Luis Angarita Azpurua, president of the Farmatodo chain, and his vice president were accused of pricing "irregularities".
They were charged under laws aimed at controlling skyrocketing inflation.
The arrests come days after President Nicolas Maduro ordered the arrests of the owners of the well-known Dia a Dia supermarket chain.
Mr Angarita and his deputy Agustin Antonio Alvarez Costa are accused of understocking shelves and of leaving cash registers unstaffed, thus causing long queues to form outside.
Prosecutors said their actions were intended to lead to speculation and rising prices, which would have a "destabilizing" effect on the economy.
News of the arrest came days after President Maduro ordered the arrest of the owners of the Dia a Dia supermarket chain on similar charges.
President of the Venezuelan Federation of Chambers of Commerce Jorge Roig said the offences the executives had been detained for were "completely subjective".
"We consider it as an attack not only on Farmatodo, but on a specific attack on private industry," he said .
In late January, thousands of Venezuelans attended an opposition march in Caracas, banging empty pots to highlight what they say is the shortage of many staple foods.
Demonstrators also voiced discontent at high inflation, crime and long queues.
Many analysts say currency controls that restrict the availability of dollars for imports play a key role in creating a scarcity of many items.
But President Maduro is adamant that many businessmen are colluding with the political opposition to oust his government.
He has accused four supermarket chains of hoarding goods and smuggling items out of the country.
Venezuela - a major oil producer - has been heavily affected by the fall in oil prices on international markets. The economy officially entered recession in December.

At a ceremony held at Stirling Castle - where the museum is located, Prince William officially launched the Thin Red Line Appeal.
The fund-raising campaign hopes to secure backing of £4m by 2019 to redevelop the museum.
The Prince said that he was "honoured" to be the patron of the appeal.
On arrival at the ceremony, the prince was met by the Earl of Mar and Kellie, hereditary keeper of Stirling Castle, who presented him with the key to the castle.
William was then escorted around the current museum by Col AK Miller, viewing key exhibits including The Thin Red Line painting which depicts the Battle of Balaclava during the Crimean War in 1854.
He spoke with pupils from the Queen Victoria School, whose parents serve in the Armed Forces - asking them about school life, their future ambitions - and also which football team they support.
During the visit, William also met Lt Col Alexander Grant, 70, who is in a painting depicting fighting in Aden, now part of Yemen, in 1967.
Mr Grant said: "He seemed to be an extremely interested individual and easy to talk to and quite pleasant to chat with."
In a speech at the ceremony, Prince William said: "I am honoured to be patron of the Thin Red Line Appeal, to ensure that the history of one of Scotland's most iconic regiments can be preserved as part of the nation's story here in Stirling."
Col Miller said: "We were very fortunate to get Prince William as patron for the Thin Red Line Appeal."
He added that since the museum lost its Ministry of Defence funding in 2012, it has been entirely self-supporting.
The museum recently received news that it is to be supported by the Heritage Lottery Fund.
The prince said he is "confident" the £4m target is achievable.
Venezuela has arrested two top executives of one of the country's largest pharmacy chains.
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Prince William has launched an appeal to secure the future of the Argyll and Sutherland Highlanders Regimental Museum in Stirling.